ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.17G>A (p.Arg6Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002407887 SCV002715024 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-14 criteria provided, single submitter clinical testing The p.R6K variant (also known as c.17G>A), located in coding exon 1 of the SDHD gene, results from a G to A substitution at nucleotide position 17. The arginine at codon 6 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, lysine is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003097253 SCV003297497 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 2023-02-06 criteria provided, single submitter clinical testing 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: 1780372). 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. This variant is present in population databases (rs770924084, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 6 of the SDHD protein (p.Arg6Lys).

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