ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.260T>C (p.Leu87Ser) (rs727504457)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697957 SCV000826592 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-04-19 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 87 of the SDHB protein (p.Leu87Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families affected with paragangliomas and/or pheochromocytomas (PMID: 11404820, 19454582, 15328326, 22517557, 12807974), as well as one healthy individual (PMID: 11404820). This variant is also known as 394T>C (L88S) and 263T>C (L88S) in the literature. ClinVar contains an entry for this variant (Variation ID: 178686). 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. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155443 SCV000205134 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2013-08-16 criteria provided, single submitter clinical testing The Leu87Ser variant in SDHB has been reported in at least 6 individuals with pa raganglioma/pheochromocytoma, one of which progressed into malignant disease (Bu rnichon 2009, Buffet 2012). In addition, this variant has been identified in 1 i n >13,000 control chromosomes (Astuti 2001, Neumann 2004, Burnichon 2009, NHLBI Exome Sequencing Project: http://evs.gs.washington.edu/EVS/). Please note that f or diseases with clinical variability, reduced penetrance, or recessive inherita nce, pathogenic variants may be present at a low frequency in the general popula tion. Computational analyses (biochemical amino acid properties, conservation, A lignGVGD, PolyPhen2, and SIFT) suggest that the Leu87Ser variant may impact the protein, though this information is not predictive enough to determine pathogeni city. In summary, this variant is likely to be pathogenic based on published dat a and a low allele frequency in control chromosomes, though additional studies a re required to fully establish its clinical significance.

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