NM_177550.5(SLC13A5):c.1006G>A (p.Gly336Ser) AND Developmental and epileptic encephalopathy, 25

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 17, 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:: RCV000800790.7

Allele description [Variation Report for NM_177550.5(SLC13A5):c.1006G>A (p.Gly336Ser)]

NM_177550.5(SLC13A5):c.1006G>A (p.Gly336Ser)

Gene:

SLC13A5:solute carrier family 13 member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_177550.5(SLC13A5):c.1006G>A (p.Gly336Ser)

HGVS:

NC_000017.11:g.6695775C>T
NG_034220.1:g.22647G>A
NM_001143838.3:c.1006G>A
NM_001284509.2:c.955G>A
NM_001284510.2:c.877G>A
NM_177550.5:c.1006G>AMANE SELECT
NP_001137310.1:p.Gly336Ser
NP_001271438.1:p.Gly319Ser
NP_001271439.1:p.Gly293Ser
NP_808218.1:p.Gly336Ser
NP_808218.1:p.Gly336Ser
LRG_1020t1:c.1006G>A
LRG_1020:g.22647G>A
LRG_1020p1:p.Gly336Ser
NC_000017.10:g.6599094C>T
NM_177550.4:c.1006G>A

Protein change:

G293S

Links:

dbSNP: rs1187250417

NCBI 1000 Genomes Browser:

rs1187250417

Molecular consequence:

NM_001143838.3:c.1006G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001284509.2:c.955G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001284510.2:c.877G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_177550.5:c.1006G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 25 (DEE25)
Synonyms:: Epileptic encephalopathy, early infantile, 25; Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta; Epileptic encephalopathy, early infantile, 25, with amelogenesis imperfecta
Identifiers:: MONDO: MONDO:0014392; MedGen: C4014621; Orphanet: 442835; OMIM: 615905

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000940524	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 4, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004562716	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Oct 17, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000940524

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 4, 2022)

germline

clinical testing

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

SCV004562716

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Oct 17, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV000940524.3

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 336 of the SLC13A5 protein (p.Gly336Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC13A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 646494). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004562716.1

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

Description

Due to limited information, including a lack of clinical and/or functional data and an uninformative population frequency, the clinical significance of this variant is uncertain at this time.

#	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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