ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.13T>C (p.Trp5Arg)

gnomAD frequency: 0.00001  dbSNP: rs778202647
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002525628 SCV000554066 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 2023-03-15 criteria provided, single submitter clinical testing 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: 412514). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. This variant is present in population databases (rs778202647, gnomAD 0.002%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 5 of the SDHD protein (p.Trp5Arg).
Ambry Genetics RCV001011375 SCV001171685 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-23 criteria provided, single submitter clinical testing The p.W5R variant (also known as c.13T>C), located in coding exon 1 of the SDHD gene, results from a T to C substitution at nucleotide position 13. The tryptophan at codon 5 is replaced by arginine, an amino acid with dissimilar 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.

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