Submissions for variant NM_003000.3(SDHB):c.598dup (p.Trp200fs)

dbSNP: rs2101516417

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001926606	SCV002207080	pathogenic	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2021-06-02	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 with SDHB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp200Leufs*22) in the SDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898).
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315451	SCV004015259	likely pathogenic	Paragangliomas 4	2023-07-07	criteria provided, single submitter	clinical testing	This insertion of one nucleotide in SDHB results in a truncated protein, p.Trp200LeufsTer22 (W200Lfs*22). Using alternate nomenclature, this variant is also known as SDHB c.598dupT. The duplication causes a frameshift, which changes Tryptophan to Leucine at codon 200 and creates a premature stop codon at position 22 downstream. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has not been reported in individuals with cancer as far as we know. This variant does not have a ClinVar entry. In-silico predictions show this variant to be deleterious. This variant is not present in the population database gnomAD. Therefore, this variant is classified as likely pathogenic.