ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3413G>A (p.Arg1138His)

gnomAD frequency: 0.00004  dbSNP: rs745801044
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000557538 SCV000648245 uncertain significance Hypertrophic cardiomyopathy 14 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1138 of the MYH6 protein (p.Arg1138His). This variant is present in population databases (rs745801044, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 32492895). ClinVar contains an entry for this variant (Variation ID: 470523). 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 with a positive predictive value of 80%. 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.
Ambry Genetics RCV002456181 SCV002614387 uncertain significance Cardiovascular phenotype 2022-04-08 criteria provided, single submitter clinical testing The p.R1138H variant (also known as c.3413G>A), located in coding exon 24 of the MYH6 gene, results from a G to A substitution at nucleotide position 3413. The arginine at codon 1138 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well 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 RCV002491072 SCV002798189 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-12-29 criteria provided, single submitter clinical testing
GeneDx RCV003233743 SCV003930636 uncertain significance not provided 2022-12-06 criteria provided, single submitter clinical testing Reported in a patient with hypertrophic cardiomyopathy (HCM) in published literature (Kim et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30681346, 32492895)
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678718 SCV000804888 uncertain significance Left ventricular noncompaction 2017-06-21 no assertion criteria provided clinical testing

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