NM_001031710.3(KLHL7):c.1051C>T (p.Arg351Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 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:: RCV001382705.15

Allele description

NM_001031710.3(KLHL7):c.1051C>T (p.Arg351Ter)

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.1051C>T (p.Arg351Ter)

HGVS:

NC_000007.14:g.23165812C>T
NG_016983.2:g.65079C>T
NM_001031710.3:c.1051C>TMANE SELECT
NM_018846.5:c.907C>T
NP_001026880.2:p.Arg351Ter
NP_061334.4:p.Arg303Ter
NC_000007.13:g.23205431C>T
NG_016983.1:g.65079C>T
NM_001031710.2:c.1051C>T
NR_033328.2:n.1424C>T

Protein change:

R303*; ARG351TER

Links:

OMIM: 611119.0009; dbSNP: rs746612410

NCBI 1000 Genomes Browser:

rs746612410

Molecular consequence:

NR_033328.2:n.1424C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001031710.3:c.1051C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_018846.5:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001581607	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 19, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30997404, 27392078, 30426380, 28492532
SCV004032727	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Sep 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581607

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 19, 2020)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004032727

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Pathogenic
(Sep 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	1	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

New macular findings in individuals with biallelic KLHL7 gene mutation.

Heng LZ, Kennedy J, Smithson S, Newbury-Ecob R, Churchill A.

BMJ Open Ophthalmol. 2019;4(1):e000234. doi: 10.1136/bmjophth-2018-000234.

PubMed [citation]

PMID:: 30997404
PMCID:: PMC6440596

Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa.

Angius A, Uva P, Buers I, Oppo M, Puddu A, Onano S, Persico I, Loi A, Marcia L, Höhne W, Cuccuru G, Fotia G, Deiana M, Marongiu M, Atalay HT, Inan S, El Assy O, Smit LM, Okur I, Boduroglu K, Utine GE, Kılıç E, et al.

Am J Hum Genet. 2016 Jul 7;99(1):236-45. doi: 10.1016/j.ajhg.2016.05.026. Erratum in: Am J Hum Genet. 2018 Apr 5;102(4):713. doi: 10.1016/j.ajhg.2018.03.020.

PubMed [citation]

PMID:: 27392078
PMCID:: PMC5005468

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001581607.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with autosomal recessive KLHL7-related conditions (PMID: 30426380, 30997404). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 804273). This variant is present in population databases (rs746612410, ExAC 0.003%). This sequence change creates a premature translational stop signal (p.Arg351*) in the KLHL7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KLHL7 are known to be pathogenic (PMID: 27392078, 30426380).

#	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, SCV004032727.9

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

Description

KLHL7: PVS1, PM2, PM3

#	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		1	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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