ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.233A>G (p.Lys78Arg) (rs774960237)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524825 SCV000630699 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-28 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 78 of the SDHB protein (p.Lys78Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs774960237, ExAC 0.002%). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 459140). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV001015225 SCV001176039 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-04 criteria provided, single submitter clinical testing The p.K78R variant (also known as c.233A>G), located in coding exon 3 of the SDHB gene, results from an A to G substitution at nucleotide position 233. The lysine at codon 78 is replaced by arginine, an amino acid with highly similar properties. This variant was detected in SDHB-deficient paragangilioma of the urinary bladder from one individual; however, its origin (germline vs. somatic) could not be determined (Park S et al. Arch. Pathol. Lab. Med., 2017 May;141:671-677). 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.

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