ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.359A>G (p.Asn120Ser)

dbSNP: rs1553177746
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633957 SCV000755230 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2024-05-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 120 of the SDHB protein (p.Asn120Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Cowden or Cowden-like syndrome (PMID: 21979946). ClinVar contains an entry for this variant (Variation ID: 528734). 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 with a negative predictive value of 95%. 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 RCV004948491 SCV005500592 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-17 criteria provided, single submitter clinical testing The p.N120S variant (also known as c.359A>G), located in coding exon 4 of the SDHB gene, results from an A to G substitution at nucleotide position 359. The asparagine at codon 120 is replaced by serine, an amino acid with highly similar properties. This variant was detected in a cohort of 47 PTEN mutation-negative Cowden syndrome-like individuals (Ni Y et al. Hum Mol Genet, 2012 Jan;21:300-10). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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