ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.7338G>T (p.Leu2446Phe)

gnomAD frequency: 0.00006  dbSNP: rs763858637
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698955 SCV000827646 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2446 of the COL12A1 protein (p.Leu2446Phe). This variant is present in population databases (rs763858637, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 576452). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL12A1 protein function with a negative predictive value of 80%. 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.
GeneDx RCV001597204 SCV001831830 uncertain significance not provided 2023-07-25 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
PreventionGenetics, part of Exact Sciences RCV004745558 SCV005349804 uncertain significance COL12A1-related disorder 2024-03-30 no assertion criteria provided clinical testing The COL12A1 c.7338G>T variant is predicted to result in the amino acid substitution p.Leu2446Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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