ClinVar Miner

Submissions for variant NM_001848.3(COL6A1):c.957+2T>C

dbSNP: rs794727060
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174303 SCV000225582 pathogenic not provided 2014-08-06 criteria provided, single submitter clinical testing
Centre de Genetique Humaine, Institut de Pathologie et de Genetique RCV002269932 SCV002553186 pathogenic Bethlem myopathy 1A 2022-05-11 criteria provided, single submitter clinical testing The c.957+2T>C substitution in COL6A1 gene (NM_001848.3) was detected in mosaic state (AF of 0.18) in the leukocytes of the probant and was not found in both parents. This subsitution affects the second nucleotide after the 3' end of exon 12, in the splice site. It was not found in GnomAD. Prediction tools indicate that the variant could inhibits the splice site and could lead to the in-frame skipping of exon 12. This was experimentally confirmed by cDNA sequencing on the EBV-immortalized leukocytes isolated from the patient. A exon 12 loss was already described in a young patient affected by Ullrich muscular dystrophy (PMID: 20976770). Carrying the variant in a mosaic state (MAF: 0.18), the proband was mildly affected (GOWERS+, mild CPK elevation, gait instability, small articulation hyperlaxity, ankle dorsiflexion limitation and mild calcaneal protrusion). In the litterature, there are few reports of parents (of affected child) carrying COL6A1 variant in mosaic state and exhibiting few or no symptoms (PMID: 25204870 patients F2M and F3M, PMID: 29419890 father of patient B6).

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