Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001167411 | SCV001329907 | uncertain significance | Primary hyperoxaluria, type II | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV001355504 | SCV001699049 | likely benign | not provided | 2024-01-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002365817 | SCV002661919 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2021-07-27 | criteria provided, single submitter | clinical testing | The p.F230L variant (also known as c.690C>A), located in coding exon 7 of the GRHPR gene, results from a C to A substitution at nucleotide position 690. The phenylalanine at codon 230 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001355504 | SCV001550413 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The GRHPR p.Phe230Leu variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs185747820) and in control databases in 35 of 282812 chromosomes at a frequency of 0.0001238 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Latino in 13 of 35428 chromosomes (freq: 0.000367), Other in 2 of 7224 chromosomes (freq: 0.000277) and European (non-Finnish) in 20 of 129138 chromosomes (freq: 0.000155), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.Phe230 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |