ClinVar Miner

Submissions for variant NM_001041.4(SI):c.5110C>T (p.Arg1704Ter)

gnomAD frequency: 0.00004  dbSNP: rs779803851
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255674 SCV000322611 pathogenic not provided 2023-02-28 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously reported as pathogenic or benign germline variant in association with an SI-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 23525077, 31589614, 26168399)
Illumina Laboratory Services, Illumina RCV000778683 SCV000915030 uncertain significance Sucrase-isomaltase deficiency 2018-04-16 criteria provided, single submitter clinical testing The SI c.5110C>T (p.Arg1704Ter) variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital sucrase-isomaltase deficiency.
Labcorp Genetics (formerly Invitae), Labcorp RCV000255674 SCV002160089 pathogenic not provided 2020-12-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with SI-related conditions. ClinVar contains an entry for this variant (Variation ID: 265618). This variant is present in population databases (rs779803851, ExAC 0.01%). This sequence change creates a premature translational stop signal (p.Arg1704*) in the SI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SI are known to be pathogenic (PMID: 16329100, 23103650, 25452324).

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