ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.818A>T (p.Tyr273Phe)

dbSNP: rs773523792
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570384 SCV000675088 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-15 criteria provided, single submitter clinical testing The p.Y273F variant (also known as c.818A>T), located in coding exon 8 of the SDHB gene, results from an A to T substitution at nucleotide position 818. The tyrosine at codon 273 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001063468 SCV001228315 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2023-05-20 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: 486424). This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 273 of the SDHB protein (p.Tyr273Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SDHB-related conditions.
All of Us Research Program, National Institutes of Health RCV004001127 SCV004839008 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-01-03 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with phenylalanine at codon 273 of the SDHB protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 2/251352 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.

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