ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.304C>T (p.His102Tyr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001049320 SCV001213365 likely pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 102 of the SDHD protein (p.His102Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with paraganglioma-pheochromocytoma syndrome (PMID: 22241717, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.His102 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10657297, 12811540, 19454582, 22025150, 22241717). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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