Submissions for variant NM_004168.4(SDHA):c.1305G>T (p.Leu435=)

gnomAD frequency: 0.01515  dbSNP: rs35964044

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000210529	SCV000266803	benign	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000242588	SCV000309987	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000376037	SCV000457031	benign	Hereditary pheochromocytoma-paraganglioma	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.
Illumina Laboratory Services, Illumina	RCV000291485	SCV000457032	benign	Leigh 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.
Illumina Laboratory Services, Illumina	RCV000346462	SCV000457033	uncertain significance	Mitochondrial complex II deficiency, nuclear type 1	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV000565630	SCV000664454	benign	Hereditary cancer-predisposing syndrome	2014-11-25	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.
GeneDx	RCV000242588	SCV000724562	benign	not specified	2017-11-13	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003114371	SCV002046445	benign	not provided	2021-03-16	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000242588	SCV002550447	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003114371	SCV003800523	benign	not provided	2023-11-03	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316166	SCV004015374	benign	Paragangliomas 5	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000242588	SCV001809339	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000242588	SCV001958197	benign	not specified		no assertion criteria provided	clinical testing