Submissions for variant NM_004168.4(SDHA):c.171dup (p.Val58fs)

dbSNP: rs1553997323

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657509	SCV000779245	likely pathogenic	not provided	2018-04-18	criteria provided, single submitter	clinical testing	This duplication of one nucleotide in SDHA is denoted c.171dupA at the cDNA level and p.Val58SerfsX4 (V58SfsX4) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAGT[dupA]GTGG. The duplication causes a frameshift which changes a Valine to a Serine at codon 58, and creates a premature stop codon at position 4 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider this duplication to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069584	SCV001234762	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2019-04-04	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 545901). Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Val58Serfs*4) in the SDHA gene. It is expected to result in an absent or disrupted protein product.