ClinVar Miner

Submissions for variant NM_058246.4(DNAJB6):c.791G>A (p.Arg264Gln)

gnomAD frequency: 0.00002  dbSNP: rs969715884
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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 RCV000812050 SCV000952352 uncertain significance Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 264 of the DNAJB6 protein (p.Arg264Gln). This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with DNAJB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 655798). 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 DNAJB6 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.
Athena Diagnostics RCV001664432 SCV001880722 uncertain significance not provided 2020-10-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844238 SCV002104037 uncertain significance not specified 2023-11-13 criteria provided, single submitter clinical testing Variant summary: DNAJB6 c.791G>A (p.Arg264Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3e-05 in 132624 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.791G>A has been reported in the literature in at least one individual affected with Joubert syndrome (Srivastava_2017). This report does not provide unequivocal conclusions about association of the variant with Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1D. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 28973549). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity RCV000812050 SCV004234375 uncertain significance Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) 2023-03-29 criteria provided, single submitter clinical testing

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