ClinVar Miner

Submissions for variant NM_031229.4(RBCK1):c.400C>T (p.Arg134Cys)

gnomAD frequency: 0.00001  dbSNP: rs146325218
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498479 SCV000589988 uncertain significance not provided 2017-05-31 criteria provided, single submitter clinical testing The R134C variant in the RBCK1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R134C 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. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R134C as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001045106 SCV001208940 uncertain significance Polyglucosan body myopathy type 1 2022-09-07 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 134 of the RBCK1 protein (p.Arg134Cys). This variant is present in population databases (rs146325218, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RBCK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 432276). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000498479 SCV001715303 uncertain significance not provided 2019-05-12 criteria provided, single submitter clinical testing

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