Submissions for variant NM_172351.3(CD46):c.1013C>T (p.Ala338Val)

gnomAD frequency: 0.01505  dbSNP: rs35366573

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000986508	SCV000353484	benign	Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	2018-03-06	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.
Mendelics	RCV000986508	SCV001135522	benign	Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	2024-04-24	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258277	SCV001435202	likely benign	Myofibrillar myopathy 6		criteria provided, single submitter	research	The heterozygous p.Ala353Val variant in CD46 has been identified in an individual with haemolytic uraemic syndrome and no known relatives with disease (PMID: 16621965), but has been identified in >6% of European (Finnish) chromosomes by ExAC (http://gnomad.broadinstitute.org/). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for haemolytic uraemic syndrome.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521712	SCV001731103	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294251	SCV002587690	benign	Atypical hemolytic-uremic syndrome	2020-09-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001521712	SCV002821453	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CD46: BP4, BS1, BS2
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702414	SCV001929725	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001702414	SCV001957016	benign	not specified		no assertion criteria provided	clinical testing