ClinVar Miner

Submissions for variant NM_001848.2(COL6A1):c.1399-3C>T (rs200095847)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724951 SCV000332694 uncertain significance not provided 2015-06-24 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000366066 SCV000436521 benign Collagen VI-related myopathy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000308987 SCV000528581 likely benign not specified 2016-06-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001037986 SCV001201424 uncertain significance Bethlem myopathy 1 2019-12-27 criteria provided, single submitter clinical testing This sequence change falls in intron 20 of the COL6A1 gene. It does not directly change the encoded amino acid sequence of the COL6A1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs200095847, ExAC 0.05%). This variant has been observed as heterozygous in individuals affected with limb-girdle muscular dystrophy (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 281741). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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