ClinVar Miner

Submissions for variant NM_031229.4(RBCK1):c.807C>G (p.Asp269Glu)

gnomAD frequency: 0.00004  dbSNP: rs111283441
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070144 SCV001235357 uncertain significance Polyglucosan body myopathy type 1 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 269 of the RBCK1 protein (p.Asp269Glu). This variant is present in population databases (rs111283441, gnomAD 0.02%). 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: 863224). 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 glutamic acid 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001070144 SCV001468358 uncertain significance Polyglucosan body myopathy type 1 2021-03-30 criteria provided, single submitter clinical testing RBCK1 NM_031229.3 exon 7 p.Asp269Glu (c.807C>G): This variant has not been reported in the literature but is present in 0.01% (4/26108) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/20-401565-C-G?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:863224). This variant amino Glutamic acid (Glu) is present in several species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV001760049 SCV001997969 uncertain significance not provided 2019-10-21 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function

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