Submissions for variant NM_004168.4(SDHA):c.403del (p.Asp135fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003070967	SCV003446647	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2022-05-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp135Thrfs*8) 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).
Myriad Genetics, Inc.	RCV003316881	SCV004019439	pathogenic	Paragangliomas 5	2023-03-01	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics	RCV003340601	SCV004059195	pathogenic	Hereditary cancer-predisposing syndrome	2023-08-30	criteria provided, single submitter	clinical testing	The c.403delG pathogenic mutation, located in coding exon 4 of the SDHA gene, results from a deletion of one nucleotide at nucleotide position 403, causing a translational frameshift with a predicted alternate stop codon (p.D135Tfs*8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.