ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.238G>A (p.Ala80Thr)

gnomAD frequency: 0.00001  dbSNP: rs149375851
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000470224 SCV000546022 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 80 of the SDHC protein (p.Ala80Thr). This variant is present in population databases (rs149375851, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 407045). 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 expected to disrupt SDHC protein function with a positive predictive value of 95%. 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 RCV002451096 SCV002738430 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-08 criteria provided, single submitter clinical testing The p.A80T variant (also known as c.238G>A), located in coding exon 4 of the SDHC gene, results from a G to A substitution at nucleotide position 238. The alanine at codon 80 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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.
All of Us Research Program, National Institutes of Health RCV004000757 SCV004829620 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 80 of the SDHC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHC-related disorders in the literature. This variant has been identified in 2/248946 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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