ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2374T>A (p.Trp792Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701680 SCV000830492 likely pathogenic Hypertrophic cardiomyopathy 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 792 of the MYBPC3 protein (p.Trp792Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). A computational algorithm designed to assess the pathogenicity of variants in MYBPC3 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). A different variant (c.2374T>A) giving rise to the same protein effect observed here (p.Trp792Arg) has been reported in multiple individuals affected with hypertrophic cardiomyopathy (PMID: 15519027, 19808356, 23074333, 27532257, 24793961, Invitae), indicating that this residue may be critical for protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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