ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.413A>G (p.Asp138Gly)

dbSNP: rs1570948527
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816787 SCV000957312 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-12-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 138 of the SDHB protein (p.Asp138Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with paraganglioma (Inviate). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 659740). 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. This variant disrupts the p.Asp138 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22517554, 31666924, 31492822). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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