Submissions for variant NM_004168.4(SDHA):c.1432+1_1432+2delinsAG

dbSNP: rs1579410180

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001011550	SCV001171883	likely pathogenic	Hereditary cancer-predisposing syndrome	2018-02-07	criteria provided, single submitter	clinical testing	The c.1432+1_1432+2delGTinsAG intronic variant, located in intron 10 of the SDHA gene, results from an in-frame from the deletion of two nucleotides and the insertion of two nucleotides at nucleotide position 1432. This nucleotide region is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Baylor Genetics	RCV003473567	SCV004202376	likely pathogenic	Dilated cardiomyopathy 1GG	2023-10-24	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004030324	SCV004930754	likely pathogenic	Paragangliomas 5	2024-02-08	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005213435	SCV005860118	likely pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-06-11	criteria provided, single submitter	clinical testing	This sequence change affects a splice site in intron 10 of the SDHA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the 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: 819198). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.