Submissions for variant NM_001041.4(SI):c.2426+1G>A

dbSNP: rs1712611940

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Human Genetics, Hannover Medical School	RCV003155534	SCV003844064	likely pathogenic	Sucrase-isomaltase deficiency	2023-03-24	criteria provided, single submitter	clinical testing	Variant is located in the donor splice site region and the selected prediction programs for mRNA splicing indicate aberrant splicing due to loss of the natural splice site. This Variant has not been listed in the LOVD shared and ClinVar databases to date. The variant has not yet been detected in the normal population (population database gnomAD). Literature data are currently not available. We identified this variant in homozygous state.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005100933	SCV005728148	likely pathogenic	not provided	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 21 of the SI gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SI are known to be pathogenic (PMID: 16329100, 23103650, 25452324). This variant is not present in population databases (gnomAD no frequency). 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: 2445615). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.