Submissions for variant NM_000091.5(COL4A3):c.3258G>A (p.Gly1086=)

gnomAD frequency: 0.00385  dbSNP: rs147085074

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000248366	SCV000302071	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000355980	SCV000428177	uncertain significance	Alport syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000248366	SCV000711814	benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Gly1086Gly in exon 38 of COL4A3: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 0.54% (361/66654) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs147085074).
Eurofins Ntd Llc (ga)	RCV000248366	SCV000861026	benign	not specified	2018-05-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000842905	SCV000984936	benign	not provided	2018-03-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000842905	SCV001101023	benign	not provided	2025-01-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001509575	SCV001716363	benign	Autosomal recessive Alport syndrome	2021-05-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000842905	SCV003916254	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	COL4A3: BP4, BP7, BS2
Ambry Genetics	RCV003352814	SCV004077771	likely benign	Inborn genetic diseases	2023-07-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc.	RCV000355980	SCV001456036	benign	Alport syndrome	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000842905	SCV001930995	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000842905	SCV001959792	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000842905	SCV001966871	likely benign	not provided		no assertion criteria provided	clinical testing