ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.388G>C (p.Ala130Pro)

gnomAD frequency: 0.00001  dbSNP: rs1312671864
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002544721 SCV000813230 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 2023-02-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 130 of the SDHD protein (p.Ala130Pro). 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. 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 SDHD protein function. ClinVar contains an entry for this variant (Variation ID: 566026). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. This variant is not present in population databases (gnomAD no frequency).
All of Us Research Program, National Institutes of Health RCV004004233 SCV004841248 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-12-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568583 SCV005056670 uncertain significance Mitochondrial complex 2 deficiency, nuclear type 3 2024-03-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV004948567 SCV005500693 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-22 criteria provided, single submitter clinical testing The p.A130P variant (also known as c.388G>C), located in coding exon 4 of the SDHD gene, results from a G to C substitution at nucleotide position 388. The alanine at codon 130 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
PreventionGenetics, part of Exact Sciences RCV003965435 SCV004783026 uncertain significance SDHD-related disorder 2024-01-26 no assertion criteria provided clinical testing The SDHD c.388G>C variant is predicted to result in the amino acid substitution p.Ala130Pro. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/566026/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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