NM_003597.5(KLF11):c.1039G>T (p.Ala347Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV002512855.4

Allele description [Variation Report for NM_003597.5(KLF11):c.1039G>T (p.Ala347Ser)]

NM_003597.5(KLF11):c.1039G>T (p.Ala347Ser)

Gene:

KLF11:KLF transcription factor 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p25.1

Genomic location:

Preferred name:

NM_003597.5(KLF11):c.1039G>T (p.Ala347Ser)

Other names:

A349S

HGVS:

NC_000002.12:g.10048376G>T
NG_017199.1:g.9822G>T
NM_001177716.2:c.988G>T
NM_001177718.2:c.988G>T
NM_003597.5:c.1039G>TMANE SELECT
NP_001171187.1:p.Ala330Ser
NP_001171189.1:p.Ala330Ser
NP_003588.1:p.Ala347Ser
NC_000002.11:g.10188503G>T
O14901:p.Ala347Ser

Protein change:

A330S; ALA349SER

Links:

UniProtKB: O14901#VAR_031524; OMIM: 603301.0001; dbSNP: rs121912645

NCBI 1000 Genomes Browser:

rs121912645

Molecular consequence:

NM_001177716.2:c.988G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001177718.2:c.988G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003597.5:c.1039G>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
SCV003259694	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 18, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 29758564, 35108381, 15774581, 23589285, 31124255, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003259694

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 18, 2024)

germline

clinical testing

PubMed (6)
[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

Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.

Kleinberger JW, Copeland KC, Gandica RG, Haymond MW, Levitsky LL, Linder B, Shuldiner AR, Tollefsen S, White NH, Pollin TI.

Genet Med. 2018 Jun;20(6):583-590. doi: 10.1038/gim.2017.150. Epub 2017 Oct 12.

PubMed [citation]

PMID:: 29758564
PMCID:: PMC5955780

Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not Be Included in Diagnostic Testing for MODY.

Laver TW, Wakeling MN, Knox O, Colclough K, Wright CF, Ellard S, Hattersley AT, Weedon MN, Patel KA.

Diabetes. 2022 May 1;71(5):1128-1136. doi: 10.2337/db21-0844.

PubMed [citation]

PMID:: 35108381
PMCID:: PMC9044126

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003259694.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 347 of the KLF11 protein (p.Ala347Ser). This variant is present in population databases (rs121912645, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of KLF11-related conditions (PMID: 15774581, 29758564, 35108381). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6498). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Experimental studies have shown that this missense change affects KLF11 function (PMID: 15774581, 23589285, 31124255). 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

Last Updated: Sep 29, 2024

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