Submissions for variant NM_002471.4(MYH6):c.3346C>T (p.Arg1116Cys)

dbSNP: rs372446459

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000995130	SCV001149139	uncertain significance	not provided	2018-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002320208	SCV002607107	uncertain significance	Cardiovascular phenotype	2021-02-03	criteria provided, single submitter	clinical testing	The p.R1116C variant (also known as c.3346C>T), located in coding exon 24 of the MYH6 gene, results from a C to T substitution at nucleotide position 3346. The arginine at codon 1116 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was detected in cardiomyopathy/arrhythmia and dilated cardiomyopathies (DCM) genetic testing cohorts; however, clinical details were limited, and additional cardiac variants were detected in some cases. (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309; Haas J et al. Eur Heart J, 2015 May;36:1123-35a). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002489492	SCV002780018	uncertain significance	Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to	2022-02-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003769336	SCV004654349	uncertain significance	Hypertrophic cardiomyopathy 14	2023-06-23	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 807077). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 25163546, 34087240). This variant is present in population databases (rs372446459, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1116 of the MYH6 protein (p.Arg1116Cys). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH6 protein function.
Clinical Genetics, Academic Medical Center	RCV000995130	SCV001920557	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000995130	SCV001971412	uncertain significance	not provided		no assertion criteria provided	clinical testing