Submissions for variant NM_000257.4(MYH7):c.5638C>T (p.Arg1880Cys)

dbSNP: rs1057522617

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000436520	SCV000528639	uncertain significance	not provided	2017-01-27	criteria provided, single submitter	clinical testing	The R1880C variant of uncertain significance has been identified in the MYH7 gene. The R1880C variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1880C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, to our knowledge no studies have been performed to determine the functional effect of the R1880C variant.
Invitae	RCV000525762	SCV000623747	uncertain significance	Hypertrophic cardiomyopathy	2024-01-08	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 1880 of the MYH7 protein (p.Arg1880Cys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of MYH7-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 386841). 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 expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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.
AiLife Diagnostics, AiLife Diagnostics	RCV000436520	SCV002502318	uncertain significance	not provided	2021-09-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002348206	SCV002652877	uncertain significance	Cardiovascular phenotype	2024-01-29	criteria provided, single submitter	clinical testing	The p.R1880C variant (also known as c.5638C>T), located in coding exon 36 of the MYH7 gene, results from a C to T substitution at nucleotide position 5638. The arginine at codon 1880 is replaced by cysteine, an amino acid with highly dissimilar properties. 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	RCV002488941	SCV002783121	uncertain significance	Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy	2021-12-03	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000436520	SCV004236704	uncertain significance	not provided	2023-02-21	criteria provided, single submitter	clinical testing