NM_001041.4(SI):c.5279G>T (p.Gly1760Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 8, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001343990.6

Allele description [Variation Report for NM_001041.4(SI):c.5279G>T (p.Gly1760Val)]

NM_001041.4(SI):c.5279G>T (p.Gly1760Val)

Gene:

SI:sucrase-isomaltase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.1

Genomic location:

Preferred name:

NM_001041.4(SI):c.5279G>T (p.Gly1760Val)

HGVS:

NC_000003.12:g.164982379C>A
NG_017043.1:g.101117G>T
NM_001041.4:c.5279G>TMANE SELECT
NP_001032.2:p.Gly1760Val
NC_000003.11:g.164700167C>A
NM_001041.3:c.5279G>T

Protein change:

G1760V

Links:

dbSNP: rs145556619

NCBI 1000 Genomes Browser:

rs145556619

Molecular consequence:

NM_001041.4:c.5279G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001538017	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29408290, 28492532
SCV001998455	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 8, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001538017

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 15, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001998455

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 8, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients.

Garcia-Etxebarria K, Zheng T, Bonfiglio F, Bujanda L, Dlugosz A, Lindberg G, Schmidt PT, Karling P, Ohlsson B, Simren M, Walter S, Nardone G, Cuomo R, Usai-Satta P, Galeazzi F, Neri M, Portincasa P, Bellini M, Barbara G, Jonkers D, Eswaran S, Chey WD, et al.

Clin Gastroenterol Hepatol. 2018 Oct;16(10):1673-1676. doi: 10.1016/j.cgh.2018.01.047. Epub 2018 Feb 21.

PubMed [citation]

PMID:: 29408290
PMCID:: PMC6103908

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001538017.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1760 of the SI protein (p.Gly1760Val). This variant is present in population databases (rs145556619, gnomAD 0.06%). This missense change has been observed in individual(s) with irritable bowel syndrome (PMID: 29408290). ClinVar contains an entry for this variant (Variation ID: 903057). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001998455.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Reported in association with susceptibility to IBS in three patients in published literature but also observed in multiple clinically unaffected individuals in published literature and large population cohorts (Garcia -Etxebarria et al., 2018; gnomAD); 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: 34426522, 32732636, 29408290, 34615726)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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