NM_000238.4(KCNH2):c.284A>C (p.Glu95Ala) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 15, 2020
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:: RCV001363747.8

Allele description [Variation Report for NM_000238.4(KCNH2):c.284A>C (p.Glu95Ala)]

NM_000238.4(KCNH2):c.284A>C (p.Glu95Ala)

Gene:

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.284A>C (p.Glu95Ala)

Other names:

p.E95A:GAA>GCA

HGVS:

NC_000007.14:g.150974734T>G
NG_008916.1:g.8193A>C
NM_000238.4:c.284A>CMANE SELECT
NM_001406755.1:c.107A>C
NM_172056.3:c.284A>C
NP_000229.1:p.Glu95Ala
NP_000229.1:p.Glu95Ala
NP_001393684.1:p.Glu36Ala
NP_742053.1:p.Glu95Ala
NP_742053.1:p.Glu95Ala
LRG_288t1:c.284A>C
LRG_288t2:c.284A>C
LRG_288:g.8193A>C
LRG_288p1:p.Glu95Ala
LRG_288p2:p.Glu95Ala
NC_000007.13:g.150671822T>G
NM_000238.2:c.284A>C
NM_000238.3:c.284A>C
NM_172056.2:c.284A>C
NR_176254.1:n.692A>C

Protein change:

E36A

Links:

dbSNP: rs794728414

NCBI 1000 Genomes Browser:

rs794728414

Molecular consequence:

NM_000238.4:c.284A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406755.1:c.107A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.284A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

Recent activity

Clear Turn Off Turn On

Chromosome neighbors for GEO Profiles (Select 125823472) (20)
GEO Profiles
Taxonomy Links for GEO Profiles (Select 125834507) (1)
Taxonomy
MAG: uncultured Rubripirellula sp. isolate S4_Bin_METABAT__212_1, whole genome s...
MAG: uncultured Rubripirellula sp. isolate S4_Bin_METABAT__212_1, whole genome shotgun sequencing project
gi|2433106816|emb|CALJHC000000000.1 HC010000000

Nucleotide
Gene Links for GEO Profiles (Select 125832588) (1)
Gene
EEA1 early endosome antigen 1 [Homo sapiens]
EEA1 early endosome antigen 1 [Homo sapiens]
Gene ID:8411

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001559872	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 15, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23098067, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001559872

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 15, 2020)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing.

Stattin EL, Boström IM, Winbo A, Cederquist K, Jonasson J, Jonsson BA, Diamant UB, Jensen SM, Rydberg A, Norberg A.

BMC Cardiovasc Disord. 2012 Oct 25;12:95. doi: 10.1186/1471-2261-12-95.

PubMed [citation]

PMID:: 23098067
PMCID:: PMC3520728

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, SCV001559872.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with suspected long QT syndrome (PMID: 23098067). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with alanine at codon 95 of the KCNH2 protein (p.Glu95Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine.

#	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

ClinVar

Relating variation to medicine