Submissions for variant NM_000091.5(COL4A3):c.4045G>A (p.Gly1349Ser)

dbSNP: rs2073401281

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069634	SCV001234813	uncertain significance	not provided	2023-03-23	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 COL4A3 protein function. ClinVar contains an entry for this variant (Variation ID: 862824). This missense change has been observed in individual(s) with COL4A3-related conditions (PMID: 33369211, 33532864). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1349 of the COL4A3 protein (p.Gly1349Ser).
Medical Genetics, University of Parma	RCV001089919	SCV001245152	likely pathogenic	Autosomal dominant Alport syndrome; Benign familial hematuria	2020-03-11	criteria provided, single submitter	clinical testing
Molecular Biology Laboratory, Fundació Puigvert	RCV001281230	SCV001425005	likely pathogenic	Autosomal recessive Alport syndrome	2020-02-01	criteria provided, single submitter	research
Natera, Inc.	RCV001833664	SCV002076427	uncertain significance	Alport syndrome	2021-10-15	no assertion criteria provided	clinical testing