Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000290137 | SCV000456680 | benign | Hypophosphatemic nephrolithiasis/osteoporosis 1 | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Gene |
RCV000414507 | SCV000491548 | uncertain significance | not provided | 2016-11-30 | criteria provided, single submitter | clinical testing | The G450S variant in the SLC34A1 gene has been reported previously in one individual with nephrolithiasis, however no second variant identified and familial segregation information was not included (Braun et al., 2016). This variant is observed in 31/8618 (0.36%) alleles from individuals of East Asian background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The G450S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G450S as a variant of uncertain significance. |
| 3billion, |
RCV001808776 | SCV002058916 | uncertain significance | Fanconi renotubular syndrome 2 | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SLC34A1 related disorder (PMID:26787776, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000273, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.955, 3CNET: 0.906, PP3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV000414507 | SCV002443449 | likely benign | not provided | 2024-12-29 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000414507 | SCV003825676 | uncertain significance | not provided | 2022-11-10 | criteria provided, single submitter | clinical testing |