U.S. flag

An official website of the United States government

NM_000218.3(KCNQ1):c.1437C>G (p.Phe479Leu) AND Long QT syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 18, 2022
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:
RCV003055554.2

Allele description

NM_000218.3(KCNQ1):c.1437C>G (p.Phe479Leu)

Genes:
KCNQ1OT1:KCNQ1 opposite strand/antisense transcript 1 [Gene - OMIM - HGNC]
KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.5
Genomic location:
Preferred name:
NM_000218.3(KCNQ1):c.1437C>G (p.Phe479Leu)
HGVS:
  • NC_000011.10:g.2662004C>G
  • NG_008935.1:g.222014C>G
  • NG_016178.2:g.42995G>C
  • NM_000218.3:c.1437C>GMANE SELECT
  • NM_001406836.1:c.1341C>G
  • NM_001406837.1:c.1167C>G
  • NM_001406838.1:c.897C>G
  • NM_181798.2:c.1056C>G
  • NP_000209.2:p.Phe479Leu
  • NP_000209.2:p.Phe479Leu
  • NP_001393765.1:p.Phe447Leu
  • NP_001393766.1:p.Phe389Leu
  • NP_001393767.1:p.Phe299Leu
  • NP_861463.1:p.Phe352Leu
  • NP_861463.1:p.Phe352Leu
  • LRG_1052t1:n.37995G>C
  • LRG_287t1:c.1437C>G
  • LRG_287t2:c.1056C>G
  • LRG_1052:g.42995G>C
  • LRG_287:g.222014C>G
  • LRG_287p1:p.Phe479Leu
  • LRG_287p2:p.Phe352Leu
  • NC_000011.9:g.2683234C>G
  • NM_000218.2:c.1437C>G
  • NM_181798.1:c.1056C>G
  • NR_002728.3:n.37995G>C
  • NR_002728.4:n.37991G>C
  • NR_040711.2:n.1330C>G
Protein change:
F299L
Molecular consequence:
  • NM_000218.3:c.1437C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.1341C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.1167C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.897C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.1056C>G - 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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003348118Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 18, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV003348118.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 479 of the KCNQ1 protein (p.Phe479Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNQ1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024