NM_172362.3(KCNH1):c.1180G>A (p.Ala394Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
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:: RCV001823512.3

Allele description [Variation Report for NM_172362.3(KCNH1):c.1180G>A (p.Ala394Thr)]

NM_172362.3(KCNH1):c.1180G>A (p.Ala394Thr)

Gene:

KCNH1:potassium voltage-gated channel subfamily H member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.2

Genomic location:

Preferred name:

NM_172362.3(KCNH1):c.1180G>A (p.Ala394Thr)

HGVS:

NC_000001.11:g.210919922C>T
NG_029777.2:g.219194G>A
NM_002238.4:c.1099G>A
NM_172362.3:c.1180G>AMANE SELECT
NP_002229.1:p.Ala367Thr
NP_758872.1:p.Ala394Thr
NC_000001.10:g.211093264C>T
NM_172362.2:c.[1180G>A]

Protein change:

A367T

Links:

dbSNP: rs2102561634

NCBI 1000 Genomes Browser:

rs2102561634

Molecular consequence:

NM_002238.4:c.1099G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172362.3:c.1180G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Zimmermann-Laband syndrome 1 (ZLS1)
Synonyms:: Laband syndrome; Gingival fibromatosis, abnormal fingers, fingernails, nose and ears, and splenomegaly; Fibromatosis gingival, hepatosplenomegaly other anomalies
Identifiers:: MONDO: MONDO:0024526; MedGen: C4551773; Orphanet: 3473; OMIM: 135500

Name:: Temple-Baraitser syndrome (TMBTS)
Synonyms:: Severe mental retardation and absent nails of hallux and pollex
Identifiers:: MONDO: MONDO:0012735; MedGen: C2678486; Orphanet: 420561; OMIM: 611816

Recent activity

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PREDICTED: Salmo trutta stromal membrane-associated protein 2-like (LOC115176296...
PREDICTED: Salmo trutta stromal membrane-associated protein 2-like (LOC115176296), mRNA
gi|1696185459|ref|XM_029736233.1|

Nucleotide
PREDICTED: Phyllostomus hastatus ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl...
PREDICTED: Phyllostomus hastatus ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5 (ST8SIA5), transcript variant X2, mRNA
gi|2177253386|ref|XM_045849811.1|

Nucleotide
SAMN10285335 (1)
SRA
Rattus norvegicus strain BN; Sprague-Dawley chromosome 13, alternate assembly Rn...
Rattus norvegicus strain BN; Sprague-Dawley chromosome 13, alternate assembly Rn_Celera, whole genome shotgun sequence
gi|109649551|gnl|ASM:GCF_000000125| f|AC_000081.1||gnl|NCBI_GENOMES|19043

Nucleotide
Taxonomy Links for Nucleotide (Select 527464242) (1)
Taxonomy

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073004	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV002073004

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Neuberg Centre For Genomic Medicine, NCGM, SCV002073004.1

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

Description

The missense variant p.A394T in KCNH1 (NM_172362.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.A394T variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.A394T missense variant is predicted to be damaging by both SIFT and PolyPhen2. The alanine residue at codon 394 of KCNH1 is conserved in all mammalian species. The nucleotide c.1180 in KCNH1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

#	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

Last Updated: Apr 6, 2024

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