Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001851719 | SCV002238343 | pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2021-10-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 6916). This premature translational stop signal has been observed in individual(s) with clinical features of paraganglioma-pheochromocytoma syndrome (PMID: 12000816, 25819804, 30050099). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp5*) in the SDHD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). |
Ambry Genetics | RCV004018584 | SCV005019724 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-13 | criteria provided, single submitter | clinical testing | The p.W5* pathogenic mutation (also known as c.14G>A), located in coding exon 1 of the SDHD gene, results from a G to A substitution at nucleotide position 14. This changes the amino acid from a tryptophan to a stop codon within coding exon 1. This mutation has been observed in multiple individuals with a personal and/or family history that is consistent with SDHD-related paraganglioma-pheochromocytoma syndrome (Neumann HP et al. N Engl J Med, 2002 May;346:1459-66; Richter S et al. Genet Med, 2019 Mar;21:705-717; White G et al. Endocr Connect, 2022 Feb;11; Ambry internal data). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
OMIM | RCV004018583 | SCV000027523 | pathogenic | Paragangliomas 1 | 2002-05-09 | no assertion criteria provided | literature only |