ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1913C>G (p.Thr638Ser)

dbSNP: rs370133236
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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 RCV002042621 SCV002293430 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2020-11-16 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 638 of the SDHA protein (p.Thr638Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHA-related conditions. 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 SDHA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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