Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000808149 | SCV000948243 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 760 of the CASR protein (p.Ile760Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with ectopic mineralization disorder (PMID: 34906475). ClinVar contains an entry for this variant (Variation ID: 652572). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702437 | SCV005205136 | uncertain significance | not specified | 2024-06-17 | criteria provided, single submitter | clinical testing | Variant summary: CASR c.2278A>T (p.Ile760Phe) results in a non-conservative amino acid change located in the GPCR family 3, C-terminal domain (IPR017978) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250870 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2278A>T has been reported in the literature in at least one individual affected with an ectopic mineralization disorder who was also compound heterozygous for variants in the ABCC6 gene (e.g. Saeidian_2022). This report does not provide unequivocal conclusions about association of the variant with Autosomal Dominant Hypocalcemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34906475). ClinVar contains an entry for this variant (Variation ID: 652572). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Genome |
RCV003483733 | SCV004228853 | not provided | Neonatal severe primary hyperparathyroidism; Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Bartter syndrome with hypocalcemia | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 02-12-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |