ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.914G>A (p.Cys305Tyr)

gnomAD frequency: 0.00001  dbSNP: rs878854638
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468097 SCV000553911 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 305 of the SDHA protein (p.Cys305Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 412387). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SDHA protein function. 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.
Ambry Genetics RCV000575963 SCV000674923 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-30 criteria provided, single submitter clinical testing The p.C305Y variant (also known as c.914G>A), located in coding exon 8 of the SDHA gene, results from a G to A substitution at nucleotide position 914. The cysteine at codon 305 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000662791 SCV000785602 uncertain significance Paragangliomas 5 2017-09-30 criteria provided, single submitter clinical testing
GeneDx RCV003313078 SCV004012301 uncertain significance not provided 2023-09-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Myriad Genetics, Inc. RCV000662791 SCV004018573 uncertain significance Paragangliomas 5 2023-04-20 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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