Submissions for variant NM_003000.3(SDHB):c.328A>T (p.Thr110Ser)

dbSNP: rs1407350591

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001302229	SCV001491428	uncertain significance	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2023-07-28	criteria provided, single submitter	clinical testing	Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1005370). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 110 of the SDHB protein (p.Thr110Ser).
Ambry Genetics	RCV002447295	SCV002611936	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-26	criteria provided, single submitter	clinical testing	The p.T110S variant (also known as c.328A>T), located in coding exon 4 of the SDHB gene, results from an A to T substitution at nucleotide position 328. The threonine at codon 110 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health	RCV004005006	SCV004834295	uncertain significance	Hereditary pheochromocytoma-paraganglioma	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with serine at codon 110 of the SDHB protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHB-related disorders in the literature. This variant has been identified in 1/251470 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.