Submissions for variant NM_003002.4(SDHD):c.284T>C (p.Leu95Pro)

dbSNP: rs80338846

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002433463	SCV002749858	pathogenic	Hereditary cancer-predisposing syndrome	2022-08-19	criteria provided, single submitter	clinical testing	The p.L95P pathogenic mutation (also known as c.284T>C), located in coding exon 3 of the SDHD gene, results from a T to C substitution at nucleotide position 284. The leucine at codon 95 is replaced by proline, an amino acid with similar properties. This alteration has been described as a Dutch founder mutation and has been identified in multiple patients and families with paragangliomas/pheochromocytomas, and was shown to segregate with disease in at least two families (Taschner PE et al. Genes Chromosomes Cancer, 2001 Jul;31:274-81; Cremers CW et al. Otol. Neurotol., 2002 Sep;23:755-9; Hensen EF et al. Clin. Genet., 2012 Mar;81:284-8; van Hulsteijn LT et al. Clin. Endocrinol. (Oxf), 2013 Dec;79:824-31; Bayley JP et al. BMC Med. Genet., 2014 Oct;15:111; Heesterman BL et al. Eur J Hum Genet, 2018 09;26:1339-1347; Richter S et al. Genet Med, 2019 03;21:705-717; Dreijerink KMA et al. J Clin Endocrinol Metab, 2019 11;104:5421-5426). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
GeneReviews	RCV000020521	SCV000040978	not provided	Hereditary pheochromocytoma-paraganglioma		no assertion provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701640	SCV001932079	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001701640	SCV001954629	pathogenic	not provided		no assertion criteria provided	clinical testing