Submissions for variant NM_004168.4(SDHA):c.464del (p.Asn155fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003808947	SCV004596574	pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2023-04-14	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.Asn155Ilefs*71) 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.	RCV004366652	SCV004930939	pathogenic	Paragangliomas 5	2024-02-21	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
PreventionGenetics, part of Exact Sciences	RCV004542276	SCV004780154	pathogenic	SDHA-related disorder	2023-11-15	no assertion criteria provided	clinical testing	The SDHA c.464delA variant is predicted to result in a frameshift and premature protein termination (p.Asn155Ilefs*71). 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. Frameshift variants in SDHA are expected to be pathogenic. This variant is interpreted as pathogenic.