Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000221327 | SCV000274061 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-06 | criteria provided, single submitter | clinical testing | The p.C11* pathogenic mutation (also known as c.33C>A), located in coding exon 1 of the SDHD gene, results from a C to A substitution at nucleotide position 33. This changes the amino acid from a cysteine to a stop codon within coding exon 1 (p.C11*). This mutation has been reported in multiple individuals diagnosed with pheochromocytoma(s) and/or extra-adrenal paraganglioma(s) (Neumann HP et al. N. Engl. J. Med. 2002 May;346(19):1459-66; Peczkowska M et al. J. Clin. Endocrinol. Metab. 2008 Dec;93(12):4818-25; Michaowska I et al. Neuroendocrinology. 2015 Mar;101:321-30; Michaowska I et al. Kardiochir Torakochirurgia Pol. 2016 Sep;13:276-282). Peczkowaka and colleagues analyzed numerous p.C11* carrier families ascertained through the European-American PGL-PCC registry. In this series, the penetrance of head and neck PGLs in mutation carriers was 100% by age 54 and haplotype analysis data supported p.C11* as a founder mutation of Polish origin (Peczkowska M et al. J. Clin. Endocrinol. Metab. 2008 Dec;93(12):4818-25). 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. |
Invitae | RCV002228012 | SCV000645369 | pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2022-10-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 6915). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with pheochromocytoma and/or paraganglioma (PMID: 12000816, 18826997, 29386252). It is commonly reported in individuals of Polish ancestry (PMID: 12000816, 18826997, 29386252). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys11*) 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). |
Institute of Human Genetics, |
RCV000007324 | SCV002044437 | pathogenic | Pheochromocytoma | 2021-12-09 | criteria provided, single submitter | clinical testing | Criteria applied: PVS1, PS4_MOD, PM2_SUP |
MGZ Medical Genetics Center | RCV002288472 | SCV002580586 | pathogenic | Paragangliomas 1 | 2021-12-28 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV002288472 | SCV004189826 | pathogenic | Paragangliomas 1 | 2023-08-29 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
OMIM | RCV000007324 | SCV000027522 | pathogenic | Pheochromocytoma | 2002-05-09 | no assertion criteria provided | literature only |