Submissions for variant NM_004168.4(SDHA):c.1661G>A (p.Arg554Gln)

gnomAD frequency: 0.00009  dbSNP: rs376391115

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226282	SCV000288121	likely benign	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565244	SCV000664643	likely benign	Hereditary cancer-predisposing syndrome	2018-07-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Counsyl	RCV000663186	SCV000786357	uncertain significance	Paragangliomas 5	2018-04-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001153644	SCV001314943	benign	Hereditary pheochromocytoma-paraganglioma	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001153645	SCV001314944	uncertain significance	Mitochondrial complex II deficiency, nuclear type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001153646	SCV001314945	uncertain significance	Leigh syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV002253311	SCV002525295	uncertain significance	not provided	2023-07-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with lung adenocarcinoma (Tian et al., 2020); This variant is associated with the following publications: (PMID: 31721094)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002267990	SCV002550448	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000663186	SCV004015398	likely benign	Paragangliomas 5	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000663186	SCV004018618	uncertain significance	Paragangliomas 5	2023-04-21	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
PreventionGenetics, part of Exact Sciences	RCV004541404	SCV004783399	likely benign	SDHA-related disorder	2023-07-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).