ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.955A>C (p.Ile319Leu) (rs377509915)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565889 SCV000674924 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Fulgent Genetics,Fulgent Genetics RCV000765829 SCV000897224 uncertain significance Leigh syndrome; Mitochondrial complex II deficiency; Dilated cardiomyopathy 1GG; Paragangliomas 5 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000462816 SCV000553879 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 319 of the SDHA protein (p.Ile319Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs377509915, ExAC 0.03%). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 412364). 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 tolerated, 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.

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