NM_018474.6(KIZ):c.226C>T (p.Arg76Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 29, 2024
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:: RCV000760516.8

Allele description [Variation Report for NM_018474.6(KIZ):c.226C>T (p.Arg76Ter)]

NM_018474.6(KIZ):c.226C>T (p.Arg76Ter)

Genes:

LOC130065509:ATAC-STARR-seq lymphoblastoid active region 17619 [Gene]
KIZ:kizuna centrosomal protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20p11.23

Genomic location:

Preferred name:

NM_018474.6(KIZ):c.226C>T (p.Arg76Ter)

Other names:

KIZ, ARG76TER (rs202210819)

HGVS:

NC_000020.11:g.21136463C>T
NG_033122.2:g.15484C>T
NM_001163022.3:c.6+4304C>T
NM_001163023.3:c.6+4304C>T
NM_001276389.2:c.169-9102C>T
NM_001352434.2:c.226C>T
NM_001352435.2:c.6+4304C>T
NM_001352436.2:c.-161C>T
NM_018474.6:c.226C>TMANE SELECT
NP_001339363.1:p.Arg76Ter
NP_060944.3:p.Arg76Ter
NC_000020.10:g.21117104C>T
NM_018474.4:c.226C>T
NM_018474.5:c.226C>T
NM_018474.6(KIZ):c.226C>TMANE SELECT
p.Arg76Ter

Protein change:

R76*; ARG76TER

Links:

OMIM: 615757.0001; dbSNP: rs202210819

NCBI 1000 Genomes Browser:

rs202210819

Molecular consequence:

NM_001352436.2:c.-161C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001163022.3:c.6+4304C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001163023.3:c.6+4304C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001276389.2:c.169-9102C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001352435.2:c.6+4304C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001352434.2:c.226C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_018474.6:c.226C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000890407	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 15, 2022)	germline	clinical testing	Citation Link,
SCV001208150	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 24680887, 28837078, 29057815, 31556760, 32052671, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000890407

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 15, 2022)

germline

clinical testing

Citation Link,

SCV001208150

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 29, 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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Whole-exome sequencing identifies KIZ as a ciliary gene associated with autosomal-recessive rod-cone dystrophy.

El Shamieh S, Neuillé M, Terray A, Orhan E, Condroyer C, Démontant V, Michiels C, Antonio A, Boyard F, Lancelot ME, Letexier M, Saraiva JP, Léveillard T, Mohand-Saïd S, Goureau O, Sahel JA, Zeitz C, Audo I.

Am J Hum Genet. 2014 Apr 3;94(4):625-33. doi: 10.1016/j.ajhg.2014.03.005. Epub 2014 Mar 27.

PubMed [citation]

PMID:: 24680887
PMCID:: PMC3980423

Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree.

Gustafson K, Duncan JL, Biswas P, Soto-Hermida A, Matsui H, Jakubosky D, Suk J, Telenti A, Frazer KA, Ayyagari R.

Genes (Basel). 2017 Aug 24;8(9). doi:pii: E210. 10.3390/genes8090210. Erratum in: Genes (Basel). 2017 Oct 23;8(10):E286. doi: 10.3390/genes8100286.

PubMed [citation]

PMID:: 28837078
PMCID:: PMC5615344

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000890407.3

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28837078, 24680887, 29057815, 30081015, 31556760, 31456290, 34662339, 36317312, 32052671)

#	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 Invitae, SCV001208150.5

#	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 creates a premature translational stop signal (p.Arg76*) in the KIZ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIZ are known to be pathogenic (PMID: 24680887, 29057815). This variant is present in population databases (rs202210819, gnomAD 0.7%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 24680887, 28837078, 29057815, 31556760, 32052671; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 128241). 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

Last Updated: Jun 23, 2024

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