Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000815729 | SCV000956197 | pathogenic | Parathyroid carcinoma | 2023-03-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg222*) in the CDC73 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDC73 are known to be pathogenic (PMID: 12434154). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 658835). This variant is also known as HPRT2 c.664C>T. This premature translational stop signal has been observed in individual(s) with hyperparathyroidism-jaw tumor syndrome as well as several individuals with primary hyperparathyroidism and primary hyperparathyroidism (PMID: 14585940, 20979880, 23029104, 23293331, 24716902, 25444225). It has also been observed to segregate with disease in related individuals. |
| Ambry Genetics | RCV002363129 | SCV002663252 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-30 | criteria provided, single submitter | clinical testing | The p.R222* pathogenic mutation (also known as c.664C>T), located in coding exon 7 of the CDC73 gene, results from a C to T substitution at nucleotide position 664. This changes the amino acid from an arginine to a stop codon within coding exon 7. This mutation has been detected in multiple patients with benign parathyroid disease or parathyroid carcinoma (Shattuck TM et al. N Engl J Med, 2003 Oct;349:1722-9; Bricaire L et al. J Clin Endocrinol Metab, 2013 Feb;98:E403-8; Mehta A et al. Surgery, 2014 Dec;156:1315-24; Kong J et al. Clin Endocrinol (Oxf), 2014 Aug;81:222-30; Wang W et al. Clin Endocrinol (Oxf), 2017 Dec;87:865-873). It has also been shown to segregate with disease in 4 affected family members in a kindred with Familial Isolated Primary Hyperparathyroidism (FIHP) (Kong J et al. Clin Endocrinol (Oxf), 2014 Aug;81:222-30). 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. |
| Fulgent Genetics, |
RCV002507424 | SCV002810495 | pathogenic | Hyperparathyroidism 1; Parathyroid carcinoma; Hyperparathyroidism 2 with jaw tumors | 2021-09-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003223680 | SCV003919391 | pathogenic | not provided | 2023-04-17 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 34426522, 28881068, 28833384, 20052758, 23293331, 19332451, 20979880, 14585940, 32590342, Marini2023[Review], 25444225, 17639063, 33778063, 23029104, 24716902) |