Submissions for variant NM_004370.6(COL12A1):c.2094G>C (p.Leu698Phe)

gnomAD frequency: 0.00001  dbSNP: rs756368336

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001223155	SCV001395290	uncertain significance	Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2	2023-07-10	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 698 of the COL12A1 protein (p.Leu698Phe). This variant is present in population databases (rs756368336, 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: 951282). 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. 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.
PreventionGenetics, part of Exact Sciences	RCV003945926	SCV004764017	uncertain significance	COL12A1-related condition	2023-11-29	criteria provided, single submitter	clinical testing	The COL12A1 c.2094G>C variant is predicted to result in the amino acid substitution p.Leu698Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0027% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.