Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000279142 | SCV000330339 | pathogenic | not provided | 2022-01-17 | 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: 27390877, 31672324, 24763815) |
| Invitae | RCV002229733 | SCV000816941 | pathogenic | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280428). This premature translational stop signal has been observed in individual(s) with clinical features of neonatal hyperparathyroidism and familial hypercalcemia hypocalciuria (PMID: 27390877, 31672324). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg544*) in the CASR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CASR are known to be pathogenic (PMID: 11807402, 14985373, 22422767). |
| Genetics and Molecular Pathology, |
RCV002272201 | SCV002556769 | pathogenic | Autosomal dominant hypocalcemia 1 | 2021-07-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002401974 | SCV002707588 | pathogenic | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-10-18 | criteria provided, single submitter | clinical testing | The p.R544* pathogenic mutation (also known as c.1630C>T), located in coding exon 5 of the CASR gene, results from a C to T substitution at nucleotide position 1630. This changes the amino acid from an arginine to a stop codon within coding exon 5. This alteration was identified in the homozygous state in multiple individuals diagnosed with severe neonatal hyperparathyroidism (Savas-Erdeve S et al. J Pediatr Endocrinol Metab, 2016 Sep;29:1103-10; Sorapipatcharoen K et al. J Paediatr Child Health, 2020 Jul;56:1144-1146). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |