ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.457A>G (p.Ile153Val) (rs1450956956)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565320 SCV000664491 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-01 criteria provided, single submitter clinical testing The p.I153V variant (also known as c.457A>G), located in coding exon 5 of the SDHB gene, results from an A to G substitution at nucleotide position 457. The isoleucine at codon 153 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position.To date, this alteration has been detected with an allele frequency of approximately 0.005% (greater than 20000alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive.Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001060686 SCV001225390 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-03-07 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 153 of the SDHB protein (p.Ile153Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 480781). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C2). 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. 5

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