Submissions for variant NM_002471.4(MYH6):c.569G>A (p.Arg190His)

dbSNP: rs1891729151

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001212937	SCV001384548	uncertain significance	Hypertrophic cardiomyopathy 14	2023-03-20	criteria provided, single submitter	clinical testing	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 MYH6 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 942862). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 190 of the MYH6 protein (p.Arg190His).
Ambry Genetics	RCV002348704	SCV002652487	uncertain significance	Cardiovascular phenotype	2022-06-09	criteria provided, single submitter	clinical testing	The p.R190H variant (also known as c.569G>A), located in coding exon 5 of the MYH6 gene, results from a G to A substitution at nucleotide position 569. The arginine at codon 190 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. 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	RCV002480701	SCV002792579	uncertain significance	Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to	2021-09-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001528495	SCV003919343	uncertain significance	not provided	2022-10-21	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528495	SCV001740326	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528495	SCV001959191	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528495	SCV001969902	uncertain significance	not provided		no assertion criteria provided	clinical testing