NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr) AND Leber congenital amaurosis 16

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 17, 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:: RCV000210435.4

Allele description [Variation Report for NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr)]

NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr)

Genes:

GIGYF2:GRB10 interacting GYF protein 2 [Gene - OMIM - HGNC]
KCNJ13:potassium inwardly rectifying channel subfamily J member 13 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr)

HGVS:

NC_000002.12:g.232771004A>G
NG_011847.1:g.78700A>G
NG_016742.1:g.10562T>C
NM_001103146.3:c.532+9568A>GMANE SELECT
NM_001103147.2:c.533-5408A>G
NM_001103148.2:c.532+9568A>G
NM_001172416.1:c.224+135T>C
NM_001172417.1:c.119T>C
NM_002242.4:c.359T>CMANE SELECT
NM_015575.4:c.532+9568A>G
NP_001165888.1:p.Ile40Thr
NP_002233.2:p.Ile120Thr
NC_000002.11:g.233635714A>G
NM_001172417.1:c.119T>C

Protein change:

I120T; ILE120THR

Links:

OMIM: 603208.0004; dbSNP: rs786205550

NCBI 1000 Genomes Browser:

rs786205550

Molecular consequence:

NM_001103146.3:c.532+9568A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001103147.2:c.533-5408A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001103148.2:c.532+9568A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001172416.1:c.224+135T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_015575.4:c.532+9568A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001172417.1:c.119T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002242.4:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Leber congenital amaurosis 16 (LCA16)
Identifiers:: MONDO: MONDO:0013613; MedGen: C3280062; Orphanet: 65; OMIM: 614186

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000266502	OMIM	no assertion criteria provided	Pathogenic (Mar 31, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004805114	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000266502

OMIM

no assertion criteria provided

Pathogenic
(Mar 31, 2016)

germline

literature only

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

SCV004805114

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 17, 2024)

germline

research

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations.

Khan AO, Bergmann C, Neuhaus C, Bolz HJ.

Ophthalmic Genet. 2015 Mar;36(1):79-84. doi: 10.3109/13816810.2014.985846. Epub 2014 Dec 5.

PubMed [citation]

PMID:: 25475713

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000266502.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 12-year-old Saudi Arabian girl and an unrelated 33-year-old Saudi man, who both exhibited vitreoretinal dystrophy and early-onset cataract (LCA16; 614186), Khan et al. (2015) identified homozygosity for a c.359T-C transition (c.359T-C, NM_002242.4) in the KCNJ13 gene, resulting in an ile120-to-thr (I120T) substitution at a highly conserved residue. The girl's affected younger sister was also homozygous for the mutation, whereas their first-cousin unaffected parents were heterozygous. Reexamination of the parents confirmed that both had 20/20 uncorrected visual acuity, with no evidence of corneal guttae or retinal degeneration.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004805114.2

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

#	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 1, 2024

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