ClinVar Miner

Submissions for variant NM_004369.4(COL6A3):c.8966-1G>C

gnomAD frequency: 0.00004  dbSNP: rs767517186
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000592070 SCV000708275 pathogenic not provided 2017-05-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000688238 SCV000815841 pathogenic Bethlem myopathy 1A 2025-01-29 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 40 of the COL6A3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs767517186, gnomAD 0.004%). Disruption of this splice site has been observed in individuals with autosomal recessive dystonia (PMID: 26004199). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant myopathy (internal data); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 192263). Studies have shown that disruption of this splice site results in skipping of exon 41, but is expected to preserve the integrity of the reading-frame (PMID: 26004199). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000592070 SCV002102643 pathogenic not provided 2022-02-27 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing, and published functional studies demonstrate skipping of exon 41 (Zech et al., 2015); Not observed at a significant frequency in large population cohorts (gnomAD); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); This variant is associated with the following publications: (PMID: 26004199, 26872670, 32037012, 34313030)
MGZ Medical Genetics Center RCV000172851 SCV002579829 pathogenic Dystonia 27 2022-06-27 criteria provided, single submitter clinical testing
Baylor Genetics RCV000172851 SCV003834916 pathogenic Dystonia 27 2021-04-28 criteria provided, single submitter clinical testing
OMIM RCV000172851 SCV000223820 pathogenic Dystonia 27 2015-06-04 no assertion criteria provided literature only

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