Submissions for variant NM_004370.6(COL12A1):c.1456C>T (p.Arg486Trp)

gnomAD frequency: 0.00001  dbSNP: rs371505180

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001302155	SCV001491349	uncertain significance	Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2	2024-04-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 486 of the COL12A1 protein (p.Arg486Trp). This variant is present in population databases (rs371505180, 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: 1005304). 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.
GenomeConnect - Invitae Patient Insights Network	RCV001535578	SCV001749570	not provided	Ullrich congenital muscular dystrophy 1A; Bethlem myopathy 2		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 09-14-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.