ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.5762A>G (p.Asp1921Gly)

gnomAD frequency: 0.00006  dbSNP: rs757348453
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001776380 SCV002012901 uncertain significance not provided 2019-07-12 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001885129 SCV002298250 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1921 of the COL12A1 protein (p.Asp1921Gly). This variant is present in population databases (rs757348453, 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: 1320401). 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001885129 SCV002496061 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2021-10-21 criteria provided, single submitter clinical testing COL12A1 NM_004370.5 exon 34 p.Asp1921Gly (c.5762A>G): This variant has not been reported in the literature but is present in 0.03% (6/15270) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/6-75133325-T-C?dataset=gnomad_r3). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Revvity Omics, Revvity RCV001776380 SCV003833402 uncertain significance not provided 2019-08-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV004611874 SCV005108849 uncertain significance Inborn genetic diseases 2024-06-07 criteria provided, single submitter clinical testing The c.5762A>G (p.D1921G) alteration is located in exon 34 (coding exon 33) of the COL12A1 gene. This alteration results from a A to G substitution at nucleotide position 5762, causing the aspartic acid (D) at amino acid position 1921 to be replaced by a glycine (G). 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.