Total submissions: 4
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, |
RCV003144531 | SCV003832810 | uncertain significance | not provided | 2020-02-12 | criteria provided, single submitter | clinical testing | |
Gene |
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) |