ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3809G>A (p.Arg1270His)

gnomAD frequency: 0.00001  dbSNP: rs767603407
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658367 SCV000780139 uncertain significance not provided 2018-05-25 criteria provided, single submitter clinical testing The R1270H variant of uncertain significance in the MYH6 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the R1270H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Revvity Omics, Revvity RCV000658367 SCV003809564 uncertain significance not provided 2019-04-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005056394 SCV005712552 uncertain significance Hypertrophic cardiomyopathy 14 2024-11-04 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 1270 of the MYH6 protein (p.Arg1270His). This variant is present in population databases (rs767603407, gnomAD 0.003%). 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: 546482). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.

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