ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.7001T>C (p.Ile2334Thr) (rs796052093)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480507 SCV000567162 pathogenic not provided 2015-08-04 criteria provided, single submitter clinical testing The I2334T variant in the COL12A1 gene has been reported previously as a de novo heterozygousvariant in a male with weakness, hypotonia, proximal joint contractures, and distal joint laxity noted in thefirst year of life. Muscle biopsy was consistent with a mild myopathy. Symptoms improved over time inthat case (Zou et al., 2014). This variant likely has a dominant negative effect and disrupts importantprotein-protein interactions (Zou et al., 2014). The I2334T substitution was not observed in approximately6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The I2334T variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position within the VWFA 4domain that is conserved across species. In silico analysis predicts this variant is probably damaging tothe protein structure/function. We interpret I2334T as a pathogenic variant.
Baylor Genetics RCV000850513 SCV000992717 likely pathogenic Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2018-10-12 criteria provided, single submitter clinical testing
OMIM RCV000186499 SCV000239879 pathogenic Bethlem myopathy 2 2014-05-01 no assertion criteria provided literature only
Institute of Human Genetics,Cologne University RCV000664222 SCV000787784 pathogenic Ullrich congenital muscular dystrophy 2 2018-04-25 no assertion criteria provided clinical testing

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