Submissions for variant NM_000092.5(COL4A4):c.1821G>A (p.Ala607=)

gnomAD frequency: 0.01262  dbSNP: rs114684841

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000392576	SCV000428112	benign	Alport syndrome	2018-01-12	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000601761	SCV000711818	benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Ala607Ala in exon 25 of COL4A4: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 4.48% (430/9600) o f African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs114684841).
GeneDx	RCV000601761	SCV000727781	benign	not specified	2018-02-16	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	RCV000962009	SCV001109071	benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294294	SCV002587277	benign	Focal segmental glomerulosclerosis	2022-08-16	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000962009	SCV005242813	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000392576	SCV001464040	benign	Alport syndrome	2020-09-16	no assertion criteria provided	clinical testing