Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000575825 | SCV000675126 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-15 | criteria provided, single submitter | clinical testing | The c.213_215delTGT variant (also known as p.V72del) is located in coding exon 3 of the SDHD gene. This variant results in an in-frame deletion of 3 nucleotides at positions 213 to 215 and removes a highly-conserved valine residue at codon 72. This alteration was identified in a patient with an extra-adrenal paraganglioma (Ambry internal data). This alteration disrupts an alpha helix immediately adjacent to a crucial heme binding site resulting in mis-orientation of key residues for modulating heme function (Sun F et al. Cell. 2005 Jul; 121(7):1043-57; Ambry internal structural data). Additionally, using the the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice donor site; however, direct evidence is unavailable. Based on the majority of available evidence to date, this alteration is likely to be pathogenic. |