Submissions for variant NM_004369.4(COL6A3):c.6210+1G>A

dbSNP: rs398124126

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080961	SCV000331158	pathogenic	not provided	2015-01-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000080961	SCV000617316	pathogenic	not provided	2022-12-05	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Different splice changes at this residue (c.6210+1G>C) and (c.6210+1G>T) and in nearby residues have been reported in the Human Gene Mutation Database and in the published literature (Stenson et al., 2014; D'Amico et al., 2017; Brias et al., 2010); This variant is associated with the following publications: (PMID: 25525159, 24907562, 15689448, 24314752, 18160674, 19015158, 22075033, 34167565, 34006472, 31127727, 35832501, 20301676, 18366090, 17785673, 20976770, 15563506)
Baylor Genetics	RCV000175056	SCV000807203	pathogenic	Ullrich congenital muscular dystrophy 1A	2017-09-01	criteria provided, single submitter	clinical testing	This mutation has been previously reported as disease-causing and was found once in our laboratory de novo in a 1-year-old female with a neuromuscular disorder: arthrogryposis, hypotonia, FTT, scoliosis, torticollis, fragile capillary syndrome.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817699	SCV000958277	pathogenic	Bethlem myopathy 1A	2024-09-24	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 16 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-related 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal dominant Ullrich congenital muscular dystrophy (PMID: 15563506). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 94956). Studies have shown that disruption of this splice site results in skipping of exon 16, but is expected to preserve the integrity of the reading-frame (PMID: 15563506). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000080961	SCV002064022	pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing	COL6A3: PS2:Very Strong, PVS1:Strong, PM1, PM2, PS4:Moderate, PS3:Supporting
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000080961	SCV005197631	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
OMIM	RCV003764764	SCV000038975	pathogenic	Ullrich congenital muscular dystrophy 1C	2009-07-07	no assertion criteria provided	literature only
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital	RCV000175056	SCV001482341	pathogenic	Ullrich congenital muscular dystrophy 1A	2019-05-31	no assertion criteria provided	research
GeneReviews	RCV000817699	SCV001519047	not provided	Bethlem myopathy 1A		no assertion provided	literature only	Common variant that results in exon 16 skipping
Clinical Genetics, Academic Medical Center	RCV000080961	SCV001924211	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000080961	SCV001954452	pathogenic	not provided		no assertion criteria provided	clinical testing