ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.1837C>T (p.Arg613Cys)

gnomAD frequency: 0.00001  dbSNP: rs759135168
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658289 SCV000780060 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing The R635C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R635C variant is observed in 5/18,866 (0.03%) alleles from individuals of East Asian background (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855370 SCV002268471 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy 2022-10-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 635 of the POMT1 protein (p.Arg635Cys). This variant is present in population databases (rs759135168, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 546416). 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 POMT1 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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