Submissions for variant NM_004168.4(SDHA):c.1526_1527delinsGA (p.Ser509Ter)

dbSNP: rs1064793567

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483714	SCV000566467	pathogenic	not provided	2017-04-27	criteria provided, single submitter	clinical testing	This variant is denoted SDHA c.1526_1527delCGinsGA at the cDNA level and p.Ser509Ter (S509X) at the protein level. The surrounding sequence is ACAT[delCG][insGA]GAAC. This in frame deletion and insertion of 2 nucleotides creates a nonsense variant, which changes a Serine to a premature stop codon. 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. We consider SDHA c.1526_1527delCGinsGA to be pathogenic.
Ambry Genetics	RCV000575106	SCV000675026	pathogenic	Hereditary cancer-predisposing syndrome	2020-11-25	criteria provided, single submitter	clinical testing	The c.1526_1527delCGinsGA pathogenic mutation, located in coding exon 11 of the SDHA gene, results from an in-frame deletion of CG and insertion of GA at nucleotide positions 1526 to 1527. This changes the amino acid from a serine to a stop codon within coding exon 11 (p.S509*). 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	RCV000800769	SCV000940501	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser509*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 418987). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004529607	SCV004110297	pathogenic	SDHA-related disorder	2023-04-07	criteria provided, single submitter	clinical testing	The SDHA c.1526_1527delinsGA variant is predicted to result in premature protein termination (p.Ser509*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in SDHA are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics	RCV003476157	SCV004200642	likely pathogenic	Dilated cardiomyopathy 1GG	2023-05-24	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004023117	SCV004933580	pathogenic	Paragangliomas 5	2024-02-08	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.