Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001150112 | SCV001311125 | uncertain significance | Sucrase-isomaltase deficiency | 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 | RCV002557230 | SCV003481940 | likely benign | not provided | 2024-01-20 | criteria provided, single submitter | clinical testing | |
| Genetics and Molecular Pathology, |
RCV001150112 | SCV004175509 | uncertain significance | Sucrase-isomaltase deficiency | 2023-04-12 | criteria provided, single submitter | clinical testing | The SI c.5279G>A variant is classified as VARIANT OF UNCERTAIN SIGNIFICANCE (PM3, PM2) The variant is a single nucleotide change in exon 47/48 of the SI gene, which is predicted to change the amino acid glycine at position 1760 in the protein to aspartic acid. The variant has been previously detected in at least one individual with Congenital sucrase-isomaltase deficiency with unclear zygosity (PMID: 32732636). The variant is in dbSNP (rs145556619) but is rare in population databases (gnomAD: 23/151954, 0 homozygote) (PM2). The variant has been reported by other laboratories or HGMD (Accession no.: CM2124321) with conflicting interpretations of pathogenicity (1 VUS, 1 Likely Benign/ Disease causing) (ClinVar Variation ID: 903058). Computational preditions are conflicting (neither BP4 or PP3 applied). The variant was detected in trans in the patient with a Likely Pathogenic variant (PM3). Clinical review is recommended. |