Submissions for variant NM_000143.4(FH):c.309C>T (p.Ala103=)

gnomAD frequency: 0.02876  dbSNP: rs10926501

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125106	SCV000168546	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	RCV000163273	SCV000213801	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	RCV000383130	SCV000356718	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.
Illumina Laboratory Services, Illumina	RCV000327050	SCV000356719	benign	Hereditary leiomyomatosis and renal cell cancer	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000327050	SCV000356720	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.
Invitae	RCV000588869	SCV000556452	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588869	SCV000695630	benign	not provided	2016-05-04	criteria provided, single submitter	clinical testing	Variant summary: The FH c.309C>T (p.Ala103Ala) variant affects a non-conserved nucleotide, resulting in a synonymous mutation with 5/5 in silico tools via Alamut predicting the variant not to have an impact on normal splicing. This variant is found in 1054/121380 control chromosomes (55 homozygotes) at a frequency of 0.0086835, which greatly exceeds the maximal expected frequency of a pathogenic allele (0.0000025), suggesting this variant is benign. In addition, clinical diagnostic laboratories classify variant as benign via ClinVar (without evidence to independently evaluate). Taken together, this variant was classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588869	SCV001159161	benign	not provided	2023-09-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000125106	SCV002047105	benign	not specified	2021-05-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163273	SCV002535555	benign	Hereditary cancer-predisposing syndrome	2020-02-24	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000125106	SCV002552153	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000327050	SCV004015717	benign	Hereditary leiomyomatosis and renal cell cancer	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000588869	SCV000802761	benign	not provided	2017-08-04	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000383130	SCV001458385	benign	Fumarase deficiency	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000125106	SCV001806954	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000125106	SCV001953232	benign	not specified		no assertion criteria provided	clinical testing