ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5645G>A (p.Arg1882His)

gnomAD frequency: 0.00001  dbSNP: rs199755234
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetics and Genomics Program, Sidra Medicine RCV001293156 SCV001434153 uncertain significance Hypertrophic cardiomyopathy criteria provided, single submitter research
GeneDx RCV001732095 SCV001982974 uncertain significance not provided 2021-04-16 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001879972 SCV002153639 uncertain significance Hypertrophic cardiomyopathy 14 2024-08-01 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 1882 of the MYH6 protein (p.Arg1882His). This variant is present in population databases (rs199755234, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 978747). 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 with a negative 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 RCV002348854 SCV002651770 uncertain significance Cardiovascular phenotype 2022-06-06 criteria provided, single submitter clinical testing The p.R1882H variant (also known as c.5645G>A), located in coding exon 35 of the MYH6 gene, results from a G to A substitution at nucleotide position 5645. The arginine at codon 1882 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.

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