rs199473452

Variant names:

• chr11-2527990-C-G
• rs199473452
• NM_000218.3:c.449C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-2527990-C-G
• chr11-2527990-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000218.3(KCNQ1):​c.449C>G​(p.Ala150Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: KCNQ1 NM_000218.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.79

Genes affected

KCNQ1 (HGNC:6294): (potassium voltage-gated channel subfamily Q member 1) This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.449C>G	p.Ala150Gly	missense_variant	Exon 2 of 16	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.449C>G	p.Ala150Gly	missense_variant	Exon 2 of 16	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Congenital long QT syndrome Other:1

-

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19862833). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	.;D;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.7	.;L;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.59	N;N;.;N
REVEL	Uncertain	0.53
Sift	Benign	0.11	T;T;.;T
Sift4G	Benign	0.33	T;T;.;T
Polyphen		0.0010	.;B;.;.
Vest4		0.76, 0.66
MutPred		0.81		.;Loss of stability (P = 0.0176);.;.;
MVP		0.92
MPC		1.1
ClinPred		0.36	T
GERP RS		4.5
Varity_R		0.26
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199473452; hg19: chr11-2549220;