Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130886 | SCV000185794 | pathogenic | Hereditary cancer-predisposing syndrome | 2013-12-05 | criteria provided, single submitter | clinical testing | ​The p.S52* pathogenic mutation (also known as c.155C>A), located in coding exon 2 of the SDHD gene, results from a C to A substitution at nucleotide position 155. This changes the amino acid from a serine to a stop codon within coding exon 2. This mutation was reported in a female patient diagnosed with multiple PGLs and a PCC, including carotid body PGLs, a left perihilar PGL, an inferior vena cava PGL, and an adrenal PCC (Fishbein, L et al. Ann Surg Oncol. 2013 May;20(5):1444-50). The patient was age 12 at initial diagnosis. In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Labcorp Genetics |
RCV002514740 | SCV000816134 | pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2018-05-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser52*) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with pheochromocytoma (PMID: 23512077). ClinVar contains an entry for this variant (Variation ID: 142068). Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic. |