Submissions for variant NM_003000.3(SDHB):c.653G>C (p.Trp218Ser)

dbSNP: rs1553177290

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000565392	SCV000664540	likely pathogenic	Hereditary cancer-predisposing syndrome	2017-02-09	criteria provided, single submitter	clinical testing	The p.W218S variant (also known as c.653G>C), located in coding exon 7 of the SDHB gene, results from a G to C substitution at nucleotide position 653. The tryptophan at codon 218 is replaced by serine, an amino acid with highly dissimilar properties. This alteration was detected in two relatives, a mother and daughter, who were both diagnosed with a paraganglioma (Bayley JP et al. BMC Med. Genet., 2006 Jan;7:1). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Furthermore, our structural analysis indicates that the variant is located in a key, sensitive region and likely to destabilize the protein structure. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529887	SCV001744135	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529887	SCV001928166	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529887	SCV001959447	pathogenic	not provided		no assertion criteria provided	clinical testing