Submissions for variant NM_004168.4(SDHA):c.1716dup (p.Leu573fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002414754	SCV002715962	pathogenic	Hereditary cancer-predisposing syndrome	2020-09-15	criteria provided, single submitter	clinical testing	The c.1716dupG pathogenic mutation, located in coding exon 13 of the SDHA gene, results from a duplication of G at nucleotide position 1716, causing a translational frameshift with a predicted alternate stop codon (p.L573Afs*30). 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	RCV003097158	SCV003252785	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2021-12-23	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.Leu573Alafs*30) 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).