ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.6309+3A>G (rs1553553327)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521476 SCV000617315 pathogenic not provided 2016-06-02 criteria provided, single submitter clinical testing The c.6309+3 A>G splice site variant has been previously reported as a single heterozygous de novo variant in an individual with moderate progressive Collagen VI myopathy (Brinas et al., 2010). It has also been previously reported in the heterozygous state, without a second variant, in two individuals with Ullrich congenital muscular dystrophy (De Palma et al., 2014; Foley et al., 2010). Sequencing of fibroblast-derived cDNA revealed that c.6309+3 A>G results in the skipping of exon 18, leading to an in-frame deletion of 9 amino acids, denoted p.Gly2095_Lys2103del (Brinas et al., 2010). Immunohistochemistry showed that this variant results in intracellular retention and reduced secretion of collagen VI in fibroblasts and muscle (Brinas et al., 2010; Foley et al., 2013). Additionally, the c.6309+3 A>G substitution occurs at a nucleotide position that is conserved in mammals and was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, c.6309+3 A>G is considered to be a pathogenic variant

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