Submissions for variant NM_000256.3(MYBPC3):c.3142C>A (p.Arg1048Ser)

dbSNP: rs11570113

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845354	SCV000987407	uncertain significance	not provided		criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001176024	SCV001339837	uncertain significance	Cardiomyopathy	2020-02-20	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with serine at codon 1048 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). Splice site prediction tools suggest that this variant may activate a cryptic splice donor site. However, this prediction has not been confirmed in published RNA studies. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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.
Invitae	RCV001235348	SCV001408029	uncertain significance	Hypertrophic cardiomyopathy	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1048 of the MYBPC3 protein (p.Arg1048Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 684798). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Clinical Genetics, Academic Medical Center	RCV000845354	SCV001918324	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000845354	SCV001927654	uncertain significance	not provided		no assertion criteria provided	clinical testing