ClinVar Miner

Submissions for variant NM_017534.6(MYH2):c.1249G>A (p.Gly417Ser)

gnomAD frequency: 0.00008  dbSNP: rs148270782
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038972 SCV001202477 uncertain significance Myopathy, proximal, and ophthalmoplegia 2024-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 417 of the MYH2 protein (p.Gly417Ser). This variant is present in population databases (rs148270782, gnomAD 0.01%). 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: 837599). 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 not expected to disrupt MYH2 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.
Baylor Genetics RCV001038972 SCV001527935 uncertain significance Myopathy, proximal, and ophthalmoplegia 2018-04-05 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity RCV001038972 SCV003809544 uncertain significance Myopathy, proximal, and ophthalmoplegia 2019-04-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV004031085 SCV004945121 uncertain significance Inborn genetic diseases 2023-12-26 criteria provided, single submitter clinical testing The c.1249G>A (p.G417S) alteration is located in exon 13 (coding exon 11) of the MYH2 gene. This alteration results from a G to A substitution at nucleotide position 1249, causing the glycine (G) at amino acid position 417 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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