Submissions for variant NM_000256.3(MYBPC3):c.823A>T (p.Ser275Cys)

gnomAD frequency: 0.00001  dbSNP: rs1224529304

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001206511	SCV001377822	uncertain significance	Hypertrophic cardiomyopathy	2022-10-29	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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 937491). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 275 of the MYBPC3 protein (p.Ser275Cys).
Color Diagnostics, LLC DBA Color Health	RCV001524001	SCV001733754	uncertain significance	Cardiomyopathy	2020-11-09	criteria provided, single submitter	clinical testing	This missense variant replaces serine with cysteine at codon 275 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/183868 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.
Clinical Genetics, Academic Medical Center	RCV001699520	SCV001926233	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001699520	SCV001963139	uncertain significance	not provided		no assertion criteria provided	clinical testing