Submissions for variant NM_000143.4(FH):c.1302C>T (p.Cys434=)

gnomAD frequency: 0.03163  dbSNP: rs2070080

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125104	SCV000168544	benign	not specified	2013-04-22	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.
Ambry Genetics	RCV000163275	SCV000213803	benign	Hereditary cancer-predisposing syndrome	2014-12-01	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000292482	SCV000356661	benign	Hereditary leiomyomatosis and renal cell cancer	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000292482	SCV000356662	benign	Hereditary leiomyomatosis and renal cell cancer	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.
Illumina Laboratory Services, Illumina	RCV000338010	SCV000356663	benign	Fumarase deficiency	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.
Invitae	RCV000589909	SCV000556439	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589909	SCV000695625	benign	not provided	2016-05-04	criteria provided, single submitter	clinical testing	Variant summary: The c.1302C>T variant affects a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts polymorphism outcome for this variant. 4/5 splice-tools in Alamut predict that this variant does not affect normal splicing. ESE finder predicts changes of binding motifs for RNA splicing enhancers. This variant is found in 1162/121368 control chromosomes (64 homozygotes) at a frequency of 0.0095742, which significantly exceeds the maximal expected frequency of a pathogenic allele (0.0000025), suggesting this variant is a benign polymorphism. In addition, multiple clinical laboratory/reputable database classified this variant as benign. Taken together, this variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589909	SCV001157020	benign	not provided	2023-09-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000125104	SCV002047103	benign	not specified	2021-05-17	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000125104	SCV002552127	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000292482	SCV004015716	benign	Hereditary leiomyomatosis and renal cell cancer	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000589909	SCV000802759	benign	not provided	2017-08-04	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000338010	SCV001457338	benign	Fumarase deficiency	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000125104	SCV001809260	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000125104	SCV001954327	benign	not specified		no assertion criteria provided	clinical testing