NM_002241.5(KCNJ10):c.265G>A (p.Val89Ile) AND EAST syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 7, 2023
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:: RCV003055339.3

Allele description [Variation Report for NM_002241.5(KCNJ10):c.265G>A (p.Val89Ile)]

NM_002241.5(KCNJ10):c.265G>A (p.Val89Ile)

Gene:

KCNJ10:potassium inwardly rectifying channel subfamily J member 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.2

Genomic location:

Preferred name:

NM_002241.5(KCNJ10):c.265G>A (p.Val89Ile)

HGVS:

NC_000001.11:g.160042268C>T
NG_016411.1:g.32904G>A
NM_002241.5:c.265G>AMANE SELECT
NP_002232.2:p.Val89Ile
NC_000001.10:g.160012058C>T

Protein change:

V89I

Molecular consequence:

NM_002241.5:c.265G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: EAST syndrome (SESAMES)
Synonyms:: SeSAME syndrome; Seizures, sensorineural deafness, ataxia, mental retardation and electrolyte imbalance; Epilepsy, ataxia, sensorineural deafness and tubulopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013005; MedGen: C2748572; Orphanet: 199343; OMIM: 612780

Recent activity

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Saccharomyces cerevisiae S288C glucose-induced degradation complex subunit VID30...
Saccharomyces cerevisiae S288C glucose-induced degradation complex subunit VID30 (VID30), partial mRNA
gi|296144831|ref|NM_001181093.1|

Nucleotide
amphiphysin isoform X11 [Danio rerio]
amphiphysin isoform X11 [Danio rerio]
gi|2800564620|ref|XP_068079477.1|

Protein
PREDICTED: Danio rerio amphiphysin (amph), transcript variant X12, mRNA
PREDICTED: Danio rerio amphiphysin (amph), transcript variant X12, mRNA
gi|2800564621|ref|XM_017357960.3|

Nucleotide
PREDICTED: Danio rerio amphiphysin (amph), transcript variant X11, mRNA
PREDICTED: Danio rerio amphiphysin (amph), transcript variant X11, mRNA
gi|2800564619|ref|XM_068223376.1|

Nucleotide
amphiphysin isoform X4 [Danio rerio]
amphiphysin isoform X4 [Danio rerio]
gi|2800564606|ref|XP_068079463.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003339499	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 7, 2023)	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

SCV003339499

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 7, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003339499.2

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

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 89 of the KCNJ10 protein (p.Val89Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. ClinVar contains an entry for this variant (Variation ID: 2123957). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNJ10 protein function with a negative predictive value of 80%. 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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