Submissions for variant NM_001846.4(COL4A2):c.4952G>A (p.Arg1651His)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002975470	SCV003282716	uncertain significance	not provided	2022-07-27	criteria provided, single submitter	clinical testing	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. 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 COL4A2 protein function. This variant has not been reported in the literature in individuals affected with COL4A2-related conditions. This variant is present in population databases (rs769994500, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1651 of the COL4A2 protein (p.Arg1651His).
Ambry Genetics	RCV004068273	SCV004929665	uncertain significance	Inborn genetic diseases	2023-12-19	criteria provided, single submitter	clinical testing	The c.4952G>A (p.R1651H) alteration is located in exon 48 (coding exon 47) of the COL4A2 gene. This alteration results from a G to A substitution at nucleotide position 4952, causing the arginine (R) at amino acid position 1651 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.