Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482545 | SCV000567251 | pathogenic | not provided | 2015-07-28 | criteria provided, single submitter | clinical testing | The R836X non-sense variant in the COL6A3 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R836X mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R836X as a pathogenic variant. |
Labcorp Genetics |
RCV000704208 | SCV000833147 | pathogenic | Bethlem myopathy 1A | 2025-01-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg836*) in the COL6A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL6A3 are known to be pathogenic (PMID: 26004199). This variant is present in population databases (rs761796175, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 419449). For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000482545 | SCV002019672 | pathogenic | not provided | 2019-01-31 | criteria provided, single submitter | clinical testing | |
Center for Genomics, |
RCV003224805 | SCV003920877 | likely pathogenic | Bethlem myopathy 1A; Ullrich congenital muscular dystrophy 1A; Dystonia 27 | 2021-03-30 | criteria provided, single submitter | clinical testing | COL6A3 NM_004369.3 exon 7 p.Arg836* (c.2506C>T): This variant has not been reported in the literature and is present in 0.0008% (1/112246) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-238285979-G-A). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. This variant is present in ClinVar (Variation ID:419449). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is predicted to cause a stopgain at this codon, resulting in protein truncation or loss of allelic expression through nonsense-mediated mRNA decay. Loss of function variants have been reported in association with disease for this gene (Brinas 2010 PMID:20976770). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic. |
Genetics Department, |
RCV004797817 | SCV005419269 | pathogenic | Bethlem myopathy 1C; Ullrich congenital muscular dystrophy 1C | 2024-05-15 | criteria provided, single submitter | clinical testing | The c.2506C>T variant in the COL6A3 gene is a nonsense variant predicted to undergo nonsense mediated decay and loss of function variants have been described as a causing mechanism for the gene (PVS1). The variant is extremely rare in gnomAD 4.1 (AF= 0.000005) (PM2). With all the available evidence, the variant is classified as likely pathogenic. |