Submissions for variant NM_004168.4(SDHA):c.549C>T (p.Gly183=)

gnomAD frequency: 0.00892  dbSNP: rs61733344

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000239367	SCV000297690	benign	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000291747	SCV000456992	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000339713	SCV000456993	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	RCV000394814	SCV000456994	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.
GeneDx	RCV000418051	SCV000520731	benign	not specified	2016-03-01	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	RCV000571465	SCV000664475	benign	Hereditary cancer-predisposing syndrome	2014-12-10	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000418051	SCV002046814	benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000418051	SCV002069743	benign	not specified	2022-01-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000571465	SCV002527753	benign	Hereditary cancer-predisposing syndrome	2021-05-06	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001800618	SCV002544921	benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	SDHA: BP4, BP7, BS1, BS2
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316320	SCV004015392	benign	Paragangliomas 5	2023-07-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001800618	SCV004564060	benign	not provided	2023-09-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000418051	SCV001808900	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000418051	SCV001958488	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000418051	SCV001974504	benign	not specified		no assertion criteria provided	clinical testing