ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.541G>A (p.Asp181Asn)

gnomAD frequency: 0.00001  dbSNP: rs201385062
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000459777 SCV000554016 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 181 of the SDHB protein (p.Asp181Asn). This variant is present in population databases (rs201385062, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 412479). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV000572523 SCV000675080 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-16 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.
GeneDx RCV003320655 SCV004025522 uncertain significance not provided 2023-07-31 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003476136 SCV004202977 uncertain significance Gastrointestinal stromal tumor 2024-03-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004002001 SCV004825126 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-11-30 criteria provided, single submitter clinical testing

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