NM_000343.4(SLC5A1):c.1672C>T (p.Arg558Cys) AND Congenital glucose-galactose malabsorption

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003041412.3

Allele description [Variation Report for NM_000343.4(SLC5A1):c.1672C>T (p.Arg558Cys)]

NM_000343.4(SLC5A1):c.1672C>T (p.Arg558Cys)

Gene:

SLC5A1:solute carrier family 5 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_000343.4(SLC5A1):c.1672C>T (p.Arg558Cys)

HGVS:

NC_000022.11:g.32104792C>T
NG_017045.1:g.66761C>T
NM_000343.4:c.1672C>TMANE SELECT
NM_001256314.2:c.1291C>T
NP_000334.1:p.Arg558Cys
NP_001243243.1:p.Arg431Cys
NC_000022.10:g.32500779C>T
NR_033411.1:n.1640C>T

Protein change:

R431C

Molecular consequence:

NM_000343.4:c.1672C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001256314.2:c.1291C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital glucose-galactose malabsorption (GGM)
Synonyms:: Glucose galactose malabsorption deficiency; Carbohydrate intolerance of glucose galactose; Complex carbohydrate intolerance; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011731; MedGen: C0268186; Orphanet: 35710; OMIM: 606824

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003444381	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20486940, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003444381

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 13, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Multiple sequence variations in SLC5A1 gene are associated with glucose-galactose malabsorption in a large cohort of Old Order Amish.

Xin B, Wang H.

Clin Genet. 2011 Jan;79(1):86-91. doi: 10.1111/j.1399-0004.2010.01440.x.

PubMed [citation]

PMID:: 20486940

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, SCV003444381.2

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

Description

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. This variant disrupts the p.Arg558 amino acid residue in SLC5A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20486940). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with glucose-galactose malabsorption (Invitae). This variant is present in population databases (rs754586981, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 558 of the SLC5A1 protein (p.Arg558Cys).

#	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

Last Updated: Sep 29, 2024

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