ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.2662G>C (p.Ala888Pro)

gnomAD frequency: 0.00006  dbSNP: rs373259425
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001295731 SCV001484673 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 888 of the COL12A1 protein (p.Ala888Pro). This variant is present in population databases (rs373259425, gnomAD 0.003%). 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: 999702). 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.
GeneDx RCV002469370 SCV002765805 uncertain significance not provided 2022-06-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen RCV002469370 SCV005050328 uncertain significance not provided 2024-05-01 criteria provided, single submitter clinical testing COL12A1: PM2
Ambry Genetics RCV004978247 SCV005557964 uncertain significance Inborn genetic diseases 2024-12-04 criteria provided, single submitter clinical testing The c.2662G>C (p.A888P) alteration is located in exon 13 (coding exon 12) of the COL12A1 gene. This alteration results from a G to C substitution at nucleotide position 2662, causing the alanine (A) at amino acid position 888 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.