NM_006516.4(SLC2A1):c.1396G>A (p.Gly466Ser) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 1, 2023
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:: RCV000766834.24

Allele description [Variation Report for NM_006516.4(SLC2A1):c.1396G>A (p.Gly466Ser)]

NM_006516.4(SLC2A1):c.1396G>A (p.Gly466Ser)

Gene:

SLC2A1:solute carrier family 2 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_006516.4(SLC2A1):c.1396G>A (p.Gly466Ser)

Other names:

p.G466S:GGC>AGC

HGVS:

NC_000001.11:g.42927124C>T
NG_008232.1:g.37053G>A
NM_006516.4:c.1396G>AMANE SELECT
NP_006507.2:p.Gly466Ser
LRG_1132:g.37053G>A
NC_000001.10:g.43392795C>T
NM_006516.2:c.1396G>A

Protein change:

G466S

Links:

dbSNP: rs138139624

NCBI 1000 Genomes Browser:

rs138139624

Molecular consequence:

NM_006516.4:c.1396G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000243018	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Aug 17, 2016)	germline	clinical testing	Citation Link,
SCV000615316	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Jan 28, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001748135	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Nov 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000243018

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Aug 17, 2016)

germline

clinical testing

Citation Link,

SCV000615316

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Jan 28, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001748135

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Nov 1, 2023)

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	2	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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000243018.12

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

Description

p.Gly466Ser (GGC>AGC): c.1396 G>A in exon 10 of the SLC2A1 gene (NM_006516.2)A variant of unknown significance has been identified in the SLC2A1 gene. The G466S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G466S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The G466S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a conserved position in the C-terminal cytoplasmic region of the SLC2A1 protein (Wang et al., 2000); however, Serine is observed at this position in one species in distant evolution. Missense mutations in nearby residues (R458W, R468W) have been reported in association with SLC2A1-related disorders, supporting the functional importance of this region of the protein. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

#	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

From Athena Diagnostics, SCV000615316.2

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

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001748135.20

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

Description

SLC2A1: PM2

#	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		2	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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