Submissions for variant NM_002471.4(MYH6):c.4769G>A (p.Arg1590His)

gnomAD frequency: 0.00001  dbSNP: rs377473560

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000806034	SCV000946014	uncertain significance	Hypertrophic cardiomyopathy 14	2023-07-30	criteria provided, single submitter	clinical testing	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 expected to disrupt MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 650808). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 33658040). This variant is present in population databases (rs377473560, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1590 of the MYH6 protein (p.Arg1590His).
Ambry Genetics	RCV004028229	SCV003753830	uncertain significance	Cardiovascular phenotype	2024-10-31	criteria provided, single submitter	clinical testing	The p.R1590H variant (also known as c.4769G>A), located in coding exon 31 of the MYH6 gene, results from a G to A substitution at nucleotide position 4769. The arginine at codon 1590 is replaced by histidine, an amino acid with highly similar properties. This variant has been reported in a hypertrophic cardiomyopathy (HCM) cohort (Chung H et al. J Cardiovasc Magn Reson, 2021 Mar;23:18). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV004808884	SCV005432526	uncertain significance	not provided	2024-09-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005012336	SCV005636742	uncertain significance	Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to	2024-06-12	criteria provided, single submitter	clinical testing