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NM_000218.3(KCNQ1):c.1142G>A (p.Cys381Tyr) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Jul 21, 2021
Review status:
criteria provided, conflicting classifications
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:
RCV000182180.5

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1142G>A (p.Cys381Tyr)]

NM_000218.3(KCNQ1):c.1142G>A (p.Cys381Tyr)

Gene:
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.1142G>A (p.Cys381Tyr)
Other names:
p.C381Y:TGC>TAC
HGVS:
  • NC_000011.10:g.2587583G>A
  • NG_008935.1:g.147593G>A
  • NM_000218.3:c.1142G>AMANE SELECT
  • NM_001406836.1:c.1046G>A
  • NM_001406837.1:c.872G>A
  • NM_001406838.1:c.602G>A
  • NM_181798.2:c.761G>A
  • NP_000209.2:p.Cys381Tyr
  • NP_000209.2:p.Cys381Tyr
  • NP_001393765.1:p.Cys349Tyr
  • NP_001393766.1:p.Cys291Tyr
  • NP_001393767.1:p.Cys201Tyr
  • NP_861463.1:p.Cys254Tyr
  • NP_861463.1:p.Cys254Tyr
  • LRG_287t1:c.1142G>A
  • LRG_287t2:c.761G>A
  • LRG_287:g.147593G>A
  • LRG_287p1:p.Cys381Tyr
  • LRG_287p2:p.Cys254Tyr
  • NC_000011.9:g.2608813G>A
  • NM_000218.2:c.1142G>A
  • NM_181798.1:c.761G>A
  • NR_040711.2:n.1035G>A
Protein change:
C201Y
Links:
dbSNP: rs368507376
NCBI 1000 Genomes Browser:
rs368507376
Molecular consequence:
  • NM_000218.3:c.1142G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406836.1:c.1046G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406837.1:c.872G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406838.1:c.602G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181798.2:c.761G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000234483GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Apr 22, 2013) 		germlineclinical testing

Citation Link,

SCV002501749AiLife Diagnostics, AiLife Diagnostics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jul 21, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical 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 GeneDx, SCV000234483.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

p.Cys381Tyr (TGC>TAC): c.1142 G>A in exon 9 of the KCNQ1 gene (NM_000218.2). The Cys381Tyr variant in the KCNQ1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Cys381Tyr results in a non-conservative amino acid subsitution of a Cysteine residue, which can affect disulfide bonding, with a Tyrosine residue at a position that is conserved across species. In silico analysis predicts Cys381Tyr is probably damaging to the protein structure/function. Mutations in nearby residues (Trp379Gly, Trp379Ser, Arg380Gly, Arg380Ser, Glu385Lys) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Furthermore, the Cys381Tyr variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. In summary, while Cys381Tyr is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in LQT panel(s).

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

From AiLife Diagnostics, AiLife Diagnostics, SCV002501749.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024