ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.541G>A (p.Asp181Asn) (rs201385062)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459777 SCV000554016 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-09-08 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 181 of the SDHB protein (p.Asp181Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs201385062, 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: 412479). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C1). 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
Ambry Genetics RCV000572523 SCV000675080 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-20 criteria provided, single submitter clinical testing The p.D181N variant (also known as c.541G>A) is located in coding exon 6 of the SDHB gene. The aspartic acid at codon 181 is replaced by asparagine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 6. 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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