Submissions for variant NM_000089.4(COL1A2):c.3772C>T (p.Arg1258Cys)

dbSNP: rs766273613

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000991602	SCV001143199	uncertain significance	not provided	2018-08-31	criteria provided, single submitter	clinical testing
Invitae	RCV001858737	SCV002107928	uncertain significance	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2023-05-12	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 804569). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs766273613, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1258 of the COL1A2 protein (p.Arg1258Cys). 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 expected to disrupt COL1A2 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.
Ambry Genetics	RCV003160118	SCV003858853	uncertain significance	Cardiovascular phenotype	2023-03-13	criteria provided, single submitter	clinical testing	The p.R1258C variant (also known as c.3772C>T), located in coding exon 51 of the COL1A2 gene, results from a C to T substitution at nucleotide position 3772. The arginine at codon 1258 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV000991602	SCV004039719	uncertain significance	not provided	2023-09-29	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD)