ClinVar Miner

Submissions for variant NM_031229.4(RBCK1):c.1189G>A (p.Val397Ile)

gnomAD frequency: 0.00010  dbSNP: rs538961301
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523610 SCV000620206 uncertain significance not provided 2017-08-18 criteria provided, single submitter clinical testing The V397I variant in the RBCK1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V397I 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 V397I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar 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 V397I as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001067575 SCV001232643 uncertain significance Polyglucosan body myopathy type 1 2023-08-17 criteria provided, single submitter clinical testing 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. 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 RBCK1 protein function. ClinVar contains an entry for this variant (Variation ID: 451493). This variant has not been reported in the literature in individuals affected with RBCK1-related conditions. This variant is present in population databases (rs538961301, gnomAD 0.02%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 397 of the RBCK1 protein (p.Val397Ile).
Ambry Genetics RCV002527627 SCV003734481 uncertain significance Inborn genetic diseases 2022-11-03 criteria provided, single submitter clinical testing The c.1189G>A (p.V397I) alteration is located in exon 9 (coding exon 9) of the RBCK1 gene. This alteration results from a G to A substitution at nucleotide position 1189, causing the valine (V) at amino acid position 397 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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