Submissions for variant NM_000256.3(MYBPC3):c.3358C>T (p.Arg1120Cys)

gnomAD frequency: 0.00001  dbSNP: rs368721523

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000547056	SCV000623591	uncertain significance	Hypertrophic cardiomyopathy	2023-12-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1120 of the MYBPC3 protein (p.Arg1120Cys). This variant is present in population databases (rs368721523, gnomAD 0.01%). This missense change has been observed in individuals with documented episodes of atrioventricular block (PMID: 30528150, 31514951). ClinVar contains an entry for this variant (Variation ID: 454326). 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 disruptive. 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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000601241	SCV000745029	uncertain significance	Hypertrophic cardiomyopathy 4	2015-09-21	criteria provided, single submitter	clinical testing
Center for Human Genetics, University of Leuven	RCV000547056	SCV000886825	uncertain significance	Hypertrophic cardiomyopathy	2018-10-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001188388	SCV001355444	uncertain significance	Cardiomyopathy	2023-04-24	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 1120 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 been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 30528150) and in an individual affected with dilated cardiomyopathy (PMID: 31514951). This variant has been identified in 7/241840 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.
GeneDx	RCV001564894	SCV001788134	uncertain significance	not provided	2021-02-09	criteria provided, single submitter	clinical testing	Has been reported in association with HCM in published literature (Gigli et al., 2019; Kouakam et al., 2019; Robyns et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 454326; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 31513939, 30528150, 31514951)
Ambry Genetics	RCV002323907	SCV002607177	uncertain significance	Cardiovascular phenotype	2018-11-08	criteria provided, single submitter	clinical testing	The p.R1120C variant (also known as c.3358C>T), located in coding exon 31 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 3358. The arginine at codon 1120 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002490930	SCV002786290	uncertain significance	Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10	2021-09-07	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001564894	SCV003817150	uncertain significance	not provided	2023-12-27	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000601241	SCV000733028	uncertain significance	Hypertrophic cardiomyopathy 4		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001564894	SCV002034685	uncertain significance	not provided		no assertion criteria provided	clinical testing