Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574656 | SCV000664470 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-06-20 | criteria provided, single submitter | clinical testing | The c.443_444delGCinsTT variant (also known as p.G148V), located in coding exon 4 of the SDHD gene, results from an in-frame deletion of GC and insertion of TT between nucleotide positions 443 and 444. This results in the substitution of a glycine for a valine residue at codon 148, an amino acid with dissimilar properties. This variant has not been previously reported in the literature. However, the c.443G>T variant, which results in the same amino acid change p.G148V, has been reported in a 49 year old German female diagnosed with a head and neck paraganglioma (Neumann et al. JAMA. 2004;292:943-951). In addition a similar alteration, the c.443G>A variant, which results in the amino acid change p.G148D, has been reported in two French families with history of paragangliomas (Benn DE et al. J Clin Endocrinol Metab. 2006;91:927-836; Timmers HJLM et al. Clin Endocrinol. 2008:68:561-566). This amino acid position is highly conserved in available species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |