ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.35G>A (p.Gly12Asp)

gnomAD frequency: 0.00001  dbSNP: rs764384503
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002528396 SCV000640160 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 2023-03-01 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 12 of the SDHD protein (p.Gly12Asp). This variant is present in population databases (rs764384503, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. ClinVar contains an entry for this variant (Variation ID: 465235). 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 SDHD 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.
Baylor Genetics RCV003476278 SCV004203096 uncertain significance Mitochondrial complex 2 deficiency, nuclear type 3 2023-09-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023999 SCV005020199 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-20 criteria provided, single submitter clinical testing The p.G12D variant (also known as c.35G>A), located in coding exon 1 of the SDHD gene, results from a G to A substitution at nucleotide position 35. The glycine at codon 12 is replaced by aspartic acid, an amino acid with 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003900170 SCV004714570 uncertain significance SDHD-related disorder 2023-12-20 no assertion criteria provided clinical testing The SDHD c.35G>A variant is predicted to result in the amino acid substitution p.Gly12Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, this variant is interpreted as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/465235/). 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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