Submissions for variant NM_000091.5(COL4A3):c.3476G>A (p.Arg1159His)

gnomAD frequency: 0.00007  dbSNP: rs145948549

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825665	SCV000967062	benign	not specified	2018-08-08	criteria provided, single submitter	clinical testing	The p.Arg1159His variant in COL4A3 is classified as benign due to a lack of cons ervation across species, including mammals. Of note, more than 10 mammals have a Histidine (His) at this position despite high nearby amino acid conservation. I n addition, computational prediction tools do not suggest a high likelihood of i mpact to the protein. It has also been identified in 0.4% (70/18864) of East Asi an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org dbSNP rs145948549). ACMG/AMP Criteria applied: BS1, BP4_Strong.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000912182	SCV001057276	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001141509	SCV001301860	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.
Natera, Inc.	RCV001274591	SCV001458851	likely benign	Autosomal dominant Alport syndrome	2020-02-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965608	SCV004783351	likely benign	COL4A3-related disorder	2023-03-15	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).