ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.10C>T (p.Leu4Phe) (rs1032016970)

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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 RCV001017297 SCV001178359 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-18 criteria provided, single submitter clinical testing The p.L4F variant (also known as c.10C>T), located in coding exon 1 of the SDHD gene, results from a C to T substitution at nucleotide position 10. The leucine at codon 4 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly 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.
Invitae RCV001343479 SCV001537465 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2020-08-14 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 4 of the SDHD protein (p.Leu4Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHD-related conditions. ClinVar contains an entry for this variant (Variation ID: 822168). 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.

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