Submissions for variant NM_000092.5(COL4A4):c.3979G>A (p.Val1327Met)

gnomAD frequency: 0.46716  dbSNP: rs2229813

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre	RCV001262386	SCV000221703	likely benign	Autosomal recessive Alport syndrome	2024-05-10	criteria provided, single submitter	research	Updated to Likely benign due to high local frequency
PreventionGenetics, part of Exact Sciences	RCV000246048	SCV000302116	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000271269	SCV000428078	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	RCV000246048	SCV000711757	benign	not specified	2016-02-02	criteria provided, single submitter	clinical testing	p.Val1327Met in exon 42 of COL4A4: This variant is not expected to have clinical significance because it has been identified in 45% (26293/58266) of European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs2229813).
GeneDx	RCV000246048	SCV000730234	benign	not specified	2017-05-09	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.
Athena Diagnostics	RCV000171504	SCV000841155	benign	not provided	2017-04-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000987043	SCV001136231	benign	X-linked Alport syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262386	SCV001440233	uncertain significance	Autosomal recessive Alport syndrome	2019-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV000171504	SCV001723254	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001262386	SCV001737190	benign	Autosomal recessive Alport syndrome	2021-05-18	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV001262386	SCV002503689	benign	Autosomal recessive Alport syndrome	2023-03-30	criteria provided, single submitter	clinical testing	Population allele frequency is 47% (rs2229813, 125,895/267,302 alleles in gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1
Natera, Inc.	RCV000271269	SCV001459920	benign	Alport syndrome	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000246048	SCV001932954	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000246048	SCV001955071	benign	not specified		no assertion criteria provided	clinical testing