Submissions for variant NM_004168.4(SDHA):c.628C>T (p.Arg210Ter)

dbSNP: rs775143272

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000649430	SCV000771258	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2023-01-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 539663). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is present in population databases (rs775143272, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg210*) in the SDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757).
Ambry Genetics	RCV001025088	SCV001187212	pathogenic	Hereditary cancer-predisposing syndrome	2022-09-01	criteria provided, single submitter	clinical testing	The p.R210* pathogenic mutation (also known as c.628C>T), located in coding exon 6 of the SDHA gene, results from a C to T substitution at nucleotide position 628. This changes the amino acid from an arginine to a stop codon within coding exon 6. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
“Giorgio Prodi” Cancer Research Center, University of Bologna	RCV001799694	SCV002026140	pathogenic	Gastrointestinal stromal tumor	2021-10-01	criteria provided, single submitter	research
Baylor Genetics	RCV003472044	SCV004202924	likely pathogenic	Dilated cardiomyopathy 1GG	2021-09-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004025783	SCV004933587	pathogenic	Paragangliomas 5	2024-02-07	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
GeneDx	RCV004721521	SCV005327771	pathogenic	not provided	2024-01-11	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35059314)