Submissions for variant NM_004168.4(SDHA):c.1494_1516del (p.Lys498fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002389756	SCV002700123	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-01	criteria provided, single submitter	clinical testing	The c.1494_1516del23 variant, located in coding exon 11 of the SDHA gene, results from a deletion of 23 nucleotides at nucleotide positions 1494 to 1516, causing a translational frameshift with a predicted alternate stop codon (p.K498Nfs*97). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003095236	SCV003216706	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2022-06-18	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). 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 sequence change creates a premature translational stop signal (p.Lys498Asnfs*97) 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).