Submissions for variant NM_003000.3(SDHB):c.445C>T (p.Gln149Ter)

dbSNP: rs876658451

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000219011	SCV000273688	pathogenic	Hereditary cancer-predisposing syndrome	2019-04-04	criteria provided, single submitter	clinical testing	The p.Q149* pathogenic mutation (also known as c.445C>T), located in coding exon 5 of the SDHB gene, results from a C to T substitution at nucleotide position 445. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This mutation has been reported in cohorts of patients with features of hereditary paraganglioma-pheocromocytoma syndrome (Jochmanova I et al. J. Cancer Res. Clin. Oncol. 2017 Aug;143:1421-1435; Andrews KA et al. J. Med. Genet. 2018 Jun;55:384-394). In addition to the clinical data presented in the literature, 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	RCV001857761	SCV002228791	pathogenic	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2024-08-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln149*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of paraganglioma and/or pheochromocytoma (PMID: 28374168, 29386252). ClinVar contains an entry for this variant (Variation ID: 230224). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV004020649	SCV004933608	pathogenic	Paragangliomas 4	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.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004696879	SCV005198194	pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing
Section on Medical Neuroendocrinolgy, National Institutes of Health	RCV000505327	SCV000599510	uncertain significance	Hereditary pheochromocytoma-paraganglioma		no assertion criteria provided	research