Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001143982 | SCV001304556 | uncertain significance | Sucrase-isomaltase deficiency | 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. |
| Invitae | RCV001858945 | SCV002178714 | uncertain significance | not provided | 2022-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1617 of the SI protein (p.Asp1617His). This variant is present in population databases (rs202225928, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SI-related conditions. ClinVar contains an entry for this variant (Variation ID: 899435). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SI protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV001143982 | SCV002779074 | uncertain significance | Sucrase-isomaltase deficiency | 2021-09-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002557066 | SCV003704009 | uncertain significance | Inborn genetic diseases | 2021-07-28 | criteria provided, single submitter | clinical testing | The c.4849G>C (p.D1617H) alteration is located in exon 42 (coding exon 41) of the SI gene. This alteration results from a G to C substitution at nucleotide position 4849, causing the aspartic acid (D) at amino acid position 1617 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |