ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3072C>A (p.Ser1024Arg)

gnomAD frequency: 0.00002  dbSNP: rs767605155
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001178479 SCV001342937 uncertain significance Cardiomyopathy 2019-08-16 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 1024 of the MYBPC3 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/246948 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003117808 SCV003786205 uncertain significance Hypertrophic cardiomyopathy 2022-06-13 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 919996). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and/or MYBPC3-related conditions (PMID: 32901917, 33658040). This variant is present in population databases (rs767605155, gnomAD 0.03%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1024 of the MYBPC3 protein (p.Ser1024Arg).
3billion RCV003152750 SCV003841984 uncertain significance Hypertrophic cardiomyopathy 4 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.81). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MYBPC3 related disorder (PMID: 32901917). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.

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