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Multiple HGVS. LRG_1074p2:p.Phe151Ser #1

Open zshuyinggg opened 1 year ago

zshuyinggg commented 1 year ago

The xml chunk for this variant is:

<ClinVarSet ID="92170773">
  <RecordStatus>current</RecordStatus>
  <Title>NM_000162.5(GCK):c.449T&gt;C (p.Phe150Ser) AND Maturity-onset diabetes of the young type 2</Title>
  <ReferenceClinVarAssertion ID="87384" DateLastUpdated="2022-04-23" DateCreated="2013-04-04">
    <ClinVarAccession Acc="RCV000029881" DateUpdated="2022-04-23" DateCreated="2013-04-04" Version="2" Type="RCV"/>
    <RecordStatus>current</RecordStatus>
    <ClinicalSignificance DateLastEvaluated="2011-08-18">
      <ReviewStatus>criteria provided, single submitter</ReviewStatus>
      <Description>Likely pathogenic</Description>
    </ClinicalSignificance>
    <Assertion Type="variation to disease"/>
    <AttributeSet>
      <Attribute Type="ModeOfInheritance" integerValue="262">Autosomal dominant inheritance</Attribute>
    </AttributeSet>
    <ObservedIn>
      <Sample>
        <Origin>germline</Origin>
        <Species TaxonomyId="9606">human</Species>
        <AffectedStatus>unknown</AffectedStatus>
      </Sample>
      <Method>
        <Purpose>assert pathogenicity</Purpose>
        <MethodType>clinical testing</MethodType>
      </Method>
      <ObservedData ID="97000563">
        <Attribute integerValue="1" Type="VariantAlleles"/>
      </ObservedData>
    </ObservedIn>
    <ObservedIn>
      <Sample>
        <Origin>germline</Origin>
        <Species TaxonomyId="9606">human</Species>
        <AffectedStatus>yes</AffectedStatus>
        <NumberTested>4</NumberTested>
      </Sample>
      <Method>
        <MethodType>curation</MethodType>
      </Method>
      <ObservedData ID="97334835">
        <Attribute integerValue="4" Type="VariantAlleles"/>
      </ObservedData>
    </ObservedIn>
    <MeasureSet Type="Variant" ID="36218" Acc="VCV000036218" Version="4">
      <Measure Type="single nucleotide variant" ID="44882">
        <Name>
          <ElementValue Type="Preferred">NM_000162.5(GCK):c.449T&gt;C (p.Phe150Ser)</ElementValue>
        </Name>
        <CanonicalSPDI>NC_000007.14:44150989:A:G</CanonicalSPDI>
        <AttributeSet>
          <Attribute Accession="LRG_1074t1" Type="HGVS, coding, LRG">LRG_1074t1:c.449T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="LRG_1074t2" Type="HGVS, coding, LRG">LRG_1074t2:c.452T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NM_033508" Version="3" Change="c.446T&gt;C" Type="HGVS, coding, RefSeq">NM_033508.3:c.446T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NM_000162" Version="5" Change="c.449T&gt;C" Type="HGVS, coding, RefSeq" MANESelect="true">NM_000162.5:c.449T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NM_001354800" Version="1" Change="c.449T&gt;C" Type="HGVS, coding, RefSeq">NM_001354800.1:c.449T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NM_033507" Version="3" Change="c.452T&gt;C" Type="HGVS, coding, RefSeq">NM_033507.3:c.452T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="LRG_1074" Type="HGVS, genomic, LRG">LRG_1074:g.52181T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NG_008847" Version="2" Change="g.52181T&gt;C" Type="HGVS, genomic, RefSeqGene">NG_008847.2:g.52181T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NC_000007" Version="14" Change="g.44150990A&gt;G" Type="HGVS, genomic, top level" integerValue="38">NC_000007.14:g.44150990A&gt;G</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NC_000007" Version="13" Change="g.44190589A&gt;G" Type="HGVS, genomic, top level, previous" integerValue="37">NC_000007.13:g.44190589A&gt;G</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NM_000162" Version="3" Change="c.449T&gt;C" Type="HGVS, previous">NM_000162.3:c.449T&gt;C</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="HGVS, protein"/>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="LRG_1074p1" Change="p.Phe150Ser" Type="HGVS, protein">LRG_1074p1:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="P35557" Change="p.Phe150Ser" Type="HGVS, protein">P35557:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="LRG_1074p2" Change="p.Phe151Ser" Type="HGVS, protein">LRG_1074p2:p.Phe151Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_277043" Version="1" Change="p.Phe149Ser" Type="HGVS, protein, RefSeq">NP_277043.1:p.Phe149Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_000153" Version="1" Change="p.Phe150Ser" Type="HGVS, protein, RefSeq">NP_000153.1:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_001341729" Version="1" Change="p.Phe150Ser" Type="HGVS, protein, RefSeq">NP_001341729.1:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_277042" Version="1" Change="p.Phe151Ser" Type="HGVS, protein, RefSeq">NP_277042.1:p.Phe151Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="MolecularConsequence">missense variant</Attribute>
          <XRef ID="SO:0001583" DB="Sequence Ontology"/>
          <XRef ID="NM_000162.5:c.449T&gt;C" DB="RefSeq"/>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="MolecularConsequence">missense variant</Attribute>
          <XRef ID="SO:0001583" DB="Sequence Ontology"/>
          <XRef ID="NM_001354800.1:c.449T&gt;C" DB="RefSeq"/>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="MolecularConsequence">missense variant</Attribute>
          <XRef ID="SO:0001583" DB="Sequence Ontology"/>
          <XRef ID="NM_033507.3:c.452T&gt;C" DB="RefSeq"/>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="MolecularConsequence">missense variant</Attribute>
          <XRef ID="SO:0001583" DB="Sequence Ontology"/>
          <XRef ID="NM_033508.3:c.446T&gt;C" DB="RefSeq"/>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="ProteinChange1LetterCode">F149S</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="ProteinChange1LetterCode">F150S</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="ProteinChange1LetterCode">F151S</Attribute>
        </AttributeSet>
        <CytogeneticLocation>7p13</CytogeneticLocation>
        <SequenceLocation Assembly="GRCh38" AssemblyAccessionVersion="GCF_000001405.38" AssemblyStatus="current" Chr="7" Accession="NC_000007.14" start="44150990" stop="44150990" display_start="44150990" display_stop="44150990" variantLength="1" positionVCF="44150990" referenceAlleleVCF="A" alternateAlleleVCF="G"/>
        <SequenceLocation Assembly="GRCh37" AssemblyAccessionVersion="GCF_000001405.25" AssemblyStatus="previous" Chr="7" Accession="NC_000007.13" start="44190589" stop="44190589" display_start="44190589" display_stop="44190589" variantLength="1" positionVCF="44190589" referenceAlleleVCF="A" alternateAlleleVCF="G"/>
        <MeasureRelationship Type="within single gene">
          <Name>
            <ElementValue Type="Preferred">glucokinase</ElementValue>
          </Name>
          <Symbol>
            <ElementValue Type="Preferred">GCK</ElementValue>
          </Symbol>
          <SequenceLocation Assembly="GRCh38" AssemblyAccessionVersion="GCF_000001405.38" AssemblyStatus="current" Chr="7" Accession="NC_000007.14" start="44143213" stop="44189439" display_start="44143213" display_stop="44189439" Strand="-"/>
          <SequenceLocation Assembly="GRCh37" AssemblyAccessionVersion="GCF_000001405.25" AssemblyStatus="previous" Chr="7" Accession="NC_000007.13" start="44183869" stop="44229021" display_start="44183869" display_stop="44229021" variantLength="45153" Strand="-"/>
          <XRef ID="2645" DB="Gene"/>
          <XRef Type="MIM" ID="138079" DB="OMIM"/>
          <XRef ID="HGNC:4195" DB="HGNC"/>
        </MeasureRelationship>
        <XRef ID="P35557#VAR_010588" DB="UniProtKB"/>
        <XRef Type="rs" ID="193922297" DB="dbSNP"/>
      </Measure>
      <Name>
        <ElementValue Type="Preferred">NM_000162.5(GCK):c.449T&gt;C (p.Phe150Ser)</ElementValue>
      </Name>
      <Name>
        <ElementValue Type="Preferred">NM_000162.5(GCK):c.449T&gt;C (p.Phe150Ser)</ElementValue>
      </Name>
      <AttributeSet>
        <Attribute Type="SubmitterVariantId">GDX:309464</Attribute>
      </AttributeSet>
      <XRef ID="CA213784" DB="ClinGen"/>
    </MeasureSet>
    <TraitSet Type="Disease" ID="6270">
      <Trait ID="5458" Type="Disease">
        <Name>
          <ElementValue Type="Preferred">Maturity-onset diabetes of the young type 2</ElementValue>
          <XRef ID="MONDO:0007453" DB="MONDO"/>
        </Name>
        <Name>
          <ElementValue Type="Alternate">MODY type 2</ElementValue>
        </Name>
        <Name>
          <ElementValue Type="Alternate">Diabetes mellitus MODY type 2</ElementValue>
        </Name>
        <Name>
          <ElementValue Type="Alternate">MODY glucokinase-related</ElementValue>
        </Name>
        <Name>
          <ElementValue Type="Alternate">Diabetes mellitus, type II, autosomal dominant</ElementValue>
        </Name>
        <Symbol>
          <ElementValue Type="Alternate">MODY2</ElementValue>
          <XRef Type="MIM" ID="125851" DB="OMIM"/>
        </Symbol>
        <AttributeSet>
          <Attribute Type="disease mechanism" integerValue="273">loss of function</Attribute>
          <XRef ID="GTR000512295" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000512817" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000552325" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000552542" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000552544" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000556820" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000556824" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000557910" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000558434" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000559250" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000568234" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000570044" DB="Genetic Testing Registry (GTR)"/>
          <XRef ID="GTR000595971" DB="Genetic Testing Registry (GTR)"/>
        </AttributeSet>
        <AttributeSet>
          <Attribute Type="GARD id" integerValue="10657"/>
          <XRef ID="10657" DB="Office of Rare Diseases"/>
        </AttributeSet>
        <Citation Type="review" Abbrev="GeneReviews">
          <ID Source="PubMed">29792621</ID>
          <ID Source="BookShelf">NBK500456</ID>
        </Citation>
        <XRef ID="MONDO:0007453" DB="MONDO"/>
        <XRef ID="C0342277" DB="MedGen"/>
        <XRef ID="552" DB="Orphanet"/>
        <XRef Type="MIM" ID="125851" DB="OMIM"/>
      </Trait>
    </TraitSet>
  </ReferenceClinVarAssertion>

Look at the section that defines the hgvs:

        <AttributeSet>
          <Attribute Accession="LRG_1074p1" Change="p.Phe150Ser" Type="HGVS, protein">LRG_1074p1:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="P35557" Change="p.Phe150Ser" Type="HGVS, protein">P35557:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="LRG_1074p2" Change="p.Phe151Ser" Type="HGVS, protein">LRG_1074p2:p.Phe151Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_277043" Version="1" Change="p.Phe149Ser" Type="HGVS, protein, RefSeq">NP_277043.1:p.Phe149Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_000153" Version="1" Change="p.Phe150Ser" Type="HGVS, protein, RefSeq">NP_000153.1:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_001341729" Version="1" Change="p.Phe150Ser" Type="HGVS, protein, RefSeq">NP_001341729.1:p.Phe150Ser</Attribute>
        </AttributeSet>
        <AttributeSet>
          <Attribute Accession="NP_277042" Version="1" Change="p.Phe151Ser" Type="HGVS, protein, RefSeq">NP_277042.1:p.Phe151Ser</Attribute>
        </AttributeSet>

And the tag that contains Uniprot ID:

        <XRef ID="P35557#VAR_010588" DB="UniProtKB"/>
zshuyinggg commented 1 year ago

LRG:

Locus Reference Genomic p1 means isoform1, p2 means isoform2. LRG_1074 LRG_1074p1----> NP_000153.1 LRG_1074p2--->NP_277042.1

Questions

  1. the two isoforms have different sequences. which to use?
  2. what are the other reference proteins? Why is there so many?