ClinVar Miner

Submissions for variant NM_004369.4(COL6A3):c.6309+1G>T

dbSNP: rs886043919
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000337392 SCV000342619 likely pathogenic not provided 2016-06-06 criteria provided, single submitter clinical testing
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000760148 SCV000889957 pathogenic Ullrich congenital muscular dystrophy 1A 2017-06-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002518040 SCV003259904 pathogenic Bethlem myopathy 1A 2022-01-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 18, but is expected to preserve the integrity of the reading-frame (PMID: 20976770). ClinVar contains an entry for this variant (Variation ID: 288503). Disruption of this splice site has been observed in individual(s) with clinical features of type VI/skeletal muscle collagenopathy (PMID: 20976770, 34167565). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 18 of the COL6A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL6A3 are known to be disease-causing for autosomal recessive COL6A3 conditions (PMID: 21280092, 20976770). However, certain variants affecting donor or acceptor splice sites in the triple helical domain of COL6A3 are expected to result in in-frame exon skipping and have been reported to cause autosomal dominant COL6A3-related conditions (PMID: 18366090).

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