Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000492559 | SCV000581227 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-09-07 | criteria provided, single submitter | clinical testing | The c.352delG pathogenic mutation, located in coding exon 4 of the SDHD gene, results from a deletion of one nucleotide at nucleotide position 352, causing a translational frameshift with a predicted alternate stop codon (p.D118Mfs*17). This alteration was identified in a patient with a SDH-deficient gastrointestinal stromal tumor (GIST) (Miettinen M et al. Am. J. Surg. Pathol., 2013 Feb;37:234-40). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
Invitae | RCV002231154 | SCV001587257 | pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2020-10-04 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with gastrointestinal stromal tumor syndrome and paraganglioma (PMID: 23282968, Invitae). ClinVar contains an entry for this variant (Variation ID: 428938). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly138 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29875428, 31492822, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SDHD gene (p.Asp118Metfs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the SDHD protein. |