Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000802402 | SCV000942233 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 11 of the CASR protein (p.Leu11Ser). This variant is present in population databases (rs200673016, gnomAD 0.003%). This missense change has been observed in individual(s) with primary hyperparathyroidism (HPT) (PMID: 15879434). ClinVar contains an entry for this variant (Variation ID: 647813). 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 tolerated. Experimental studies have shown that this missense change affects CASR function (PMID: 15879434). 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. |
Illumina Laboratory Services, |
RCV001146802 | SCV001307561 | uncertain significance | Familial hypoparathyroidism | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001146803 | SCV001307562 | uncertain significance | Autosomal dominant hypocalcemia 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001146804 | SCV001307563 | uncertain significance | Neonatal severe primary hyperparathyroidism | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001147690 | SCV001308531 | uncertain significance | Familial hypocalciuric hypercalcemia 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Ambry Genetics | RCV002325547 | SCV002611236 | uncertain significance | Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis | 2022-06-09 | criteria provided, single submitter | clinical testing | The p.L11S variant (also known as c.32T>C), located in coding exon 1 of the CASR gene, results from a T to C substitution at nucleotide position 32. The leucine at codon 11 is replaced by serine, an amino acid with dissimilar properties. This variant was detected in an individual with primary hyperparathyroidism and hypercalcemia, and it was reported in two affected siblings; in vitro studies indicated that this alteration may impact protein function (Pidasheva S et al. Hum Mol Genet, 2005 Jun;14:1679-90). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002507390 | SCV002814408 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2022-05-26 | criteria provided, single submitter | clinical testing |