ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.503T>C (p.Val168Ala) (rs727505267)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156792 SCV000206513 likely benign not specified 2014-09-24 criteria provided, single submitter clinical testing Val168Ala in exon 4 of MYBPC3: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, 8 mammals (Chinese tree shrew, dolphin, killer whale, cat, dog, ferret, elep hant, manatee) have an alanine (Ala) at this position despite high nearby amino acid conservation. In addition, this variant was predicted to be benign using a computational tool clinically validated by our laboratory. This tool's benign pr ediction is estimated to be correct 89% of the time (Jordan 2011).
Invitae RCV000811160 SCV000951413 uncertain significance Hypertrophic cardiomyopathy 2018-11-15 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 168 of the MYBPC3 protein (p.Val168Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs727505267, ExAC 0.02%). This variant has not been reported in the literature in individuals with MYBPC3-related disease. ClinVar contains an entry for this variant (Variation ID: 179989). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV000157303 SCV000207035 uncertain significance Catecholaminergic polymorphic ventricular tachycardia type 1 2014-08-22 no assertion criteria provided clinical testing

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