Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001120088 | SCV001278551 | uncertain significance | Hereditary spherocytosis type 5 | 2018-01-13 | 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. |
| Mayo Clinic Laboratories, |
RCV001508384 | SCV001714507 | uncertain significance | not provided | 2020-04-06 | criteria provided, single submitter | clinical testing | |
| Jiangsu Institute of Hematology, |
RCV001120088 | SCV002500001 | pathogenic | Hereditary spherocytosis type 5 | 2022-03-01 | criteria provided, single submitter | research | |
| ARUP Laboratories, |
RCV001120088 | SCV004564880 | uncertain significance | Hereditary spherocytosis type 5 | 2023-11-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987785 | SCV004804022 | uncertain significance | not specified | 2024-01-31 | criteria provided, single submitter | clinical testing | Variant summary: EPB42 c.1131G>T (p.Gln377His) results in a non-conservative amino acid change in the encoded protein sequence. Five 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-05 in 251378 control chromosomes. c.1131G>T has been reported in the literature in a homozygous and a compound heterozygous individual affected with Hereditary spherocytosis (e.g. Wang_2022). These data indicate that the variant may be associated with disease. 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: 36203343). ClinVar contains an entry for this variant (Variation ID: 887393). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |