ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.287C>T (p.Thr96Ile) (rs377620054)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569754 SCV000674939 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761150 SCV000891066 uncertain significance B Lymphoblastic Leukemia/Lymphoma with Hypodiploidy 2017-07-10 no assertion criteria provided clinical testing
Counsyl RCV000663057 SCV000786109 uncertain significance Paragangliomas 5 2018-02-26 criteria provided, single submitter clinical testing
Invitae RCV000231817 SCV000288134 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 96 of the SDHA protein (p.Thr96Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs377620054, ExAC 0.001%). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 239666). 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.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786220 SCV000924958 uncertain significance not provided 2016-05-27 no assertion criteria provided provider interpretation p.Thr96Ile (c.287C>T) in exon 3 of the SDHA gene (NM_004168.2) Seen in a patient with multiple unexplained VF arrests. Given the lack of case data and the poor fit for the phenotype, we consider this a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing").

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