ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2234A>G (p.Asp745Gly) (rs727503190)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000201877 SCV000256665 uncertain significance Familial hypertrophic cardiomyopathy 1 2015-07-02 criteria provided, single submitter research The MYBPC3 Asp745Gly variant has not been reported in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/au). We have identified the MYBPC3 Asp745Gly variant in an HCM proband where one additional MYBPC3 (Pro873His) variant of uncertain significance has also been observed (Ingles J., et al 2005). This proband was diagnosed with HCM at 18 years, has asymmetric hypertrophy with a maximal wall thickness of 30mm and has received appropriate therapy from his ICD. Segregation analysis showed this proband's affected sister to also carry both variants. In silico tools (SIFT, PolyPhen2, MutationTaster) support a deleterious role but is not sufficient enough to determine pathogenicity. We cannot rule out its possible role in disease but due to limited evidence, we class this variant as one of "uncertain significance".
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151101 SCV000198864 uncertain significance not specified 2013-07-29 criteria provided, single submitter clinical testing The Asp745Gly variant in MYBPC3 has been reported in 1 individual with HCM (Ingl es 2005) who carried another variant of unknown significance in MYBPC3, and has not been identified in large population studies. Computational analyses (biochem ical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugges t that the Asp745Gly variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In addition, splicing predicti on models suggest that this variant also create an alternative splice site, thou gh additional studies are needed to determine if this variant actually impacts s plicing. In summary, additional information is needed to fully assess the clinic al significance of the Asp745Gly variant.
OMIM RCV000023053 SCV000044344 pathogenic Familial hypertrophic cardiomyopathy 4 2007-09-01 no assertion criteria provided literature only

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