ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.1030C>T (p.His344Tyr) (rs727504392)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154556 SCV000204229 likely pathogenic Hypertrophic cardiomyopathy 2013-02-08 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000223800 SCV000280422 uncertain significance not specified 2013-11-03 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.His344Tyr (aka H344Y c.1030C>T) in PRKAG2. The variant is novel. This is a non-conservative amino acid change with a positively charged histidine residue being changed to an uncharged tyrosine. In silico analysis with PolyPhen-2 predicts the variant to be possibly damaging. The histidine at codon 344 is conserved across species, as are neighboring amino acids. I was unable to find other variants at or near this codon associated with disease (however there is no large database of PRKAG2 variants). In total the variant has not been seen in ~6300 publicly available population datasets. There is no variation at codon 344 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6300 Caucasian and African American individuals (as of October 4th, 2012). Of note, there is no non-synonymous variation from codon 263 to 419, suggesting that this region is critical for function of the kinase. There is also no variation at this codon listed in dbSNP or 1000 genomes (as of October 3rd 2012).

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