ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1286C>T (p.Ala429Val) (rs370412052)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035384 SCV000059032 uncertain significance not specified 2016-08-19 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala429Val var iant in MYBPC3 has been identified in at least 4 individuals with HCM (Gruner 20 11, Waldmuller 2011, LMM data). This variant has also been identified in 0.2% (1 5/8188) of African American chromosomes by the Exome Aggregation Consortium (ExA C,; dbSNP rs370412052). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Ala4 29Val variant is uncertain, its frequency suggests that it is more likely to be benign.
GeneDx RCV000766329 SCV000208363 uncertain significance not provided 2017-06-07 criteria provided, single submitter clinical testing The A429V variant has been reported as a novel variant in one individual with HCM (Waldmüller et al., 2011). This substitution occurs at a position that is conserved across most species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the NHLBI Exome Sequencing Project, the 1000 Genomes Project, and the Exome Aggregation Consortium (ExAC) report that A429V is present in 0.1-0.2% of alleles in individuals of African background. A429V has also been reported as a variant of uncertain significance in an individual with apical HCM (Gruner et al., 2011), and has been classified as a variant of uncertain significance by another clinical laboratory in ClinVar (Landrum et al., 2014). Finally, the A429V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000228463 SCV000284209 likely benign Hypertrophic cardiomyopathy 2017-12-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000253298 SCV000318977 uncertain significance Cardiovascular phenotype 2016-08-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000777794 SCV000913781 likely benign Cardiomyopathy 2018-10-10 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148664 SCV000190388 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research

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