Submissions for variant NM_000092.5(COL4A4):c.4656G>A (p.Met1552Ile)

gnomAD frequency: 0.01346  dbSNP: rs77104306

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000400087	SCV000428066	benign	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 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.
Athena Diagnostics Inc	RCV000517669	SCV000612970	benign	not specified	2017-05-05	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000517669	SCV000711824	benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Met1552Ile in exon 47 of COL4A4: This variant is not expected to have clinical significance because it has been identified in 4.72% (458/9710) of African chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs77104306).
GeneDx	RCV000842036	SCV000984029	benign	not provided	2018-04-26	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.
Invitae	RCV000842036	SCV001109068	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294290	SCV002587275	benign	Focal segmental glomerulosclerosis	2022-08-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000400087	SCV002078858	likely benign	Alport syndrome	2019-12-03	no assertion criteria provided	clinical testing