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: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae 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

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