ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.4705C>T (p.Pro1569Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003087852 SCV003472419 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2024-08-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1569 of the COL12A1 protein (p.Pro1569Ser). This variant is not present in population databases (gnomAD no frequency). 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: 2161058). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV004071944 SCV004928488 uncertain significance Inborn genetic diseases 2023-10-31 criteria provided, single submitter clinical testing The c.4705C>T (p.P1569S) alteration is located in exon 26 (coding exon 25) of the COL12A1 gene. This alteration results from a C to T substitution at nucleotide position 4705, causing the proline (P) at amino acid position 1569 to be replaced by a serine (S). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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