ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.226A>G (p.Thr76Ala)

gnomAD frequency: 0.00003  dbSNP: rs370684538
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
Invitae RCV000695634 SCV000824145 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 76 of the COL12A1 protein (p.Thr76Ala). This variant is present in population databases (rs370684538, gnomAD 0.002%). 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: 573860). 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.
Ambry Genetics RCV002532317 SCV003535374 uncertain significance Inborn genetic diseases 2022-08-26 criteria provided, single submitter clinical testing The c.226A>G (p.T76A) alteration is located in exon 4 (coding exon 3) of the COL12A1 gene. This alteration results from a A to G substitution at nucleotide position 226, causing the threonine (T) at amino acid position 76 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003144531 SCV003832810 uncertain significance not provided 2020-02-12 criteria provided, single submitter clinical testing
GeneDx RCV003144531 SCV003930197 uncertain significance not provided 2022-11-30 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; This variant is associated with the following publications: (PMID: 30760837)

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.