ClinVar Miner

Submissions for variant NM_017534.6(MYH2):c.4442G>A (p.Arg1481His)

gnomAD frequency: 0.00022  dbSNP: rs199751037
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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 RCV000794881 SCV000934315 uncertain significance Myopathy, proximal, and ophthalmoplegia 2025-01-12 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 1481 of the MYH2 protein (p.Arg1481His). This variant is present in population databases (rs199751037, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MYH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 641606). 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) indicates that this missense variant is expected to disrupt MYH2 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 RCV002535913 SCV003710809 uncertain significance Inborn genetic diseases 2022-08-08 criteria provided, single submitter clinical testing The c.4442G>A (p.R1481H) alteration is located in exon 32 (coding exon 30) of the MYH2 gene. This alteration results from a G to A substitution at nucleotide position 4442, causing the arginine (R) at amino acid position 1481 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000794881 SCV003809471 uncertain significance Myopathy, proximal, and ophthalmoplegia 2023-12-01 criteria provided, single submitter clinical testing
Human Genetics Bochum, Ruhr University Bochum RCV000794881 SCV004704491 uncertain significance Myopathy, proximal, and ophthalmoplegia 2023-04-18 criteria provided, single submitter clinical testing ACMG criteria used to clasify this variant: PP3_MOD
GeneDx RCV004789194 SCV005401540 uncertain significance not provided 2024-05-12 criteria provided, single submitter clinical testing 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

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