Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000326057 | SCV000441959 | uncertain significance | Sucrase-isomaltase deficiency | 2017-04-27 | criteria provided, single submitter | clinical testing | The SI c.4099A>G (p.Arg1367Gly) missense variant has been reported in one study in which it was found in one individual with congenital sucrase-isomaltase deficiency in a compound heterozygous state along with a frameshift variant (Sander et al. 2006). Control data are unavailable for this variant, but it is reported at a frequency of 0.00047 in the European American population of the Exome Sequencing Project. The evidence for this variant is limited. The p.Arg1367Gly variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for congenital sucrose-isomaltase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Fulgent Genetics, |
RCV000326057 | SCV001752563 | likely pathogenic | Sucrase-isomaltase deficiency | 2021-06-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001753808 | SCV001986316 | uncertain significance | not provided | 2020-06-22 | criteria provided, single submitter | clinical testing | Identified in at least one patient with irritable bowel syndrome with diarrhea in published literature (Garcia-Etxebarria et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16329100, 29408290) |
| Labcorp Genetics |
RCV001753808 | SCV002250224 | likely pathogenic | not provided | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1367 of the SI protein (p.Arg1367Gly). This variant is present in population databases (rs143388292, gnomAD 0.05%). This missense change has been observed in individual(s) with sucrase-isomaltase deficiency and irritable bowel syndrome (PMID: 16329100, 29408290, 32732636). ClinVar contains an entry for this variant (Variation ID: 344017). Invitae Evidence 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 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |