NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 13, 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:: RCV000079374.23

Allele description [Variation Report for NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val)]

NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val)

Gene:

KLHL7:kelch like family member 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p15.3

Genomic location:

Preferred name:

NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val)

HGVS:

NC_000007.14:g.23140784C>T
NG_016983.2:g.40051C>T
NM_001031710.3:c.458C>TMANE SELECT
NM_018846.5:c.314C>T
NP_001026880.2:p.Ala153Val
NP_001026880.2:p.Ala153Val
NP_061334.4:p.Ala105Val
NC_000007.13:g.23180403C>T
NG_016983.1:g.40051C>T
NM_001031710.2:c.458C>T
NR_033328.2:n.831C>T
Q8IXQ5:p.Ala153Val

Protein change:

A105V; ALA153VAL

Links:

UniProtKB: Q8IXQ5#VAR_060674; OMIM: 611119.0002; dbSNP: rs137853113

NCBI 1000 Genomes Browser:

rs137853113

Molecular consequence:

NM_001031710.3:c.458C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_018846.5:c.314C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_033328.2:n.831C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000111244	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 16, 2013)	germline	clinical testing	Citation Link,
SCV001397681	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19520207, 21828050, 28492532
SCV001762021	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000111244

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Aug 16, 2013)

germline

clinical testing

Citation Link,

SCV001397681

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001762021

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 17, 2021)

germline

clinical testing

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

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	1	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in a BTB-Kelch protein, KLHL7, cause autosomal-dominant retinitis pigmentosa.

Friedman JS, Ray JW, Waseem N, Johnson K, Brooks MJ, Hugosson T, Breuer D, Branham KE, Krauth DS, Bowne SJ, Sullivan LS, Ponjavic V, Gränse L, Khanna R, Trager EH, Gieser LM, Hughbanks-Wheaton D, Cojocaru RI, Ghiasvand NM, Chakarova CF, Abrahamson M, Göring HH, et al.

Am J Hum Genet. 2009 Jun;84(6):792-800. doi: 10.1016/j.ajhg.2009.05.007.

PubMed [citation]

PMID:: 19520207
PMCID:: PMC2694974

Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation.

Kigoshi Y, Tsuruta F, Chiba T.

J Biol Chem. 2011 Sep 23;286(38):33613-21. doi: 10.1074/jbc.M111.245126. Epub 2011 Aug 2.

PubMed [citation]

PMID:: 21828050
PMCID:: PMC3190939

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000111244.8

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

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001397681.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 153 of the KLHL7 protein (p.Ala153Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 19520207). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1009). 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 disruptive. Experimental studies have shown that this missense change affects KLHL7 function (PMID: 21828050). For these reasons, this variant has been classified as Pathogenic.

#	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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001762021.1

#	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	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 26, 2025

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