Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000894838 | SCV001038847 | likely benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001104499 | SCV001261372 | uncertain significance | Primary hyperoxaluria type 3 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271595 | SCV002556255 | uncertain significance | not specified | 2022-06-29 | criteria provided, single submitter | clinical testing | Variant summary: HOGA1 c.554C>T (p.Thr185Met) results in a non-conservative amino acid change in 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 0.00056 in 251482 control chromosomes (gnomAD), predominantly at a frequency of 0.0052 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 4-fold the estimated maximal expected allele frequency for a pathogenic variant in HOGA1 causing Primary Hyperoxaluria, Type III phenotype (0.0015), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.554C>T has been reported in the literature in at least two compound heterozygous individuals affected with Primary Hyperoxaluria, Type III (e.g. He_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Two laboratories classified the variant as uncertain significance and one classified it as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
| Natera, |
RCV001104499 | SCV001456950 | uncertain significance | Primary hyperoxaluria type 3 | 2020-04-11 | no assertion criteria provided | clinical testing |