Variant detail

KCNQ1C34R

c.100T>C · residue 34 · Chr11 2466428

Technical Plain language

HGVS annotation

ClinVar-style identity and transcript context

ClinVar-style HGVS

NM_000218.3(KCNQ1):c.100T>C (C34R)

HGVSc

c.100T>C

cDNA change

c.100T>C

RefSeq transcript

NM_000218.3

Ensembl transcript

ENST00000155840.12

Protein HGVS

C34R

Genomic coordinate

NC_000011.10:g.2466428T>C

ClinVar annotation

Not annotated in local ClinVar field

LQT1 penetrance Moderate risk

20% 90% credible interval 4-43%

0%20%50%100%

Limited evidence · n=0 0 observed LQT1 carriers · 1.98 hypothetical affected and 8.02 hypothetical unaffected

One-sentence summary

Roughly 1 in 4 people who carry C34R are estimated to eventually be diagnosed with Long QT type 1 — moderate risk penetrance, based on 0 carriers reported so far.

Structure: Mild_Hotspot. Functional class: NA.

Executive summary

Sources used for interpretation

The LQT1 penetrance estimate combines observed carrier counts with a feature-based model starting point. Other rows summarize supporting annotations for interpretation; not every row is a direct input to the model.

Estimatemodel output Observedmeasured in people/assays Model inputassumed, not observed Predictedcomputational Externalthird-party

EstimateModel-based penetrance estimate20% · Moderate risk

Model inputHypothetical observations1.98 affected · 8.02 unaffected

ObservedObserved carriers (literature + cohorts)0 · Limited evidence

ObservedPopulation observations (gnomAD v4)0 alleles

PredictedIn silico predictorsREVEL · PolyPhen-2 · PROVEAN

ObservedFunctional classNA

PredictedStructural contextMild_Hotspot

ExternalAutomated ACMG reviewNot a classification

ExternalExternal databasesClinVar · gnomAD · UniProt

Evidence

Carriers observed

0 LQT1 · 0 unaffected/other · 0 gnomAD

Model prior: 1.98 hypothetical affected · 8.02 hypothetical unaffected

Limited evidence

Functional data

0 published functional studies

Predictors and density

REVELUncertain0.344range 0-1

LQT1 densitySparse region0.173range 0-1

PolyPhen-2Benign0range 0-1

PROVEANNeutral-0.46cutoff <= -2.5

BLAST-PSSM-1lower = less tolerated

Overall1/5

Range labels show the expected scale or cutoff. Calls are rough orientation from published cutoffs (hover a row) — not a clinical classification.

Automated ACMG/AMP review prompts

Generated from available data — not a clinical classification

PS3not met

Published functional studies available

PM1review

Hotspot or high LQT1 density

PM2met · moderate

Absent or extremely rare in population data

PP3not met

Computational predictors support effect

BS1not met

Allele frequency too high for disorder

Reported carrier data

Paper / cohort	Carriers	LQT1 / affected	Unaffected / ambiguous	Other observations	Variant context
gnomAD population observations (v4)	0	0 LQT1	0	Population observations; not known affected cases.	gnomAD v4 allele count.
Combined literature, cohort, and gnomAD	0	0 LQT1	0	Combined totals used in the penetrance estimate.	Curated carrier totals for this variant.
Hypothetical observations from model prior (not observed patients)	10	1.98 hypothetical LQT1 affected	8.02 hypothetical unaffected	Feature-based pseudo-counts added before observed carriers.	Model input; not literature or gnomAD evidence.

Model starting point. The penetrance model starts with 1.98 hypothetical affected and 8.02 hypothetical unaffected observations derived from variant features, then updates that starting point with the real carrier counts above. As observed carrier counts grow, this feature-based starting point has less influence.

Nearby variants · researcher detail

Neighbour residue	Distance (A)	Observed variants
34	0.0
33	3.8
35	3.8
32	5.4
36	5.4
31	6.6
37	6.6
30	7.6
38	7.6
29	8.5
39	8.5
28	9.3
40	9.3
27	10.1
41	10.1
26	10.7
42	10.7
25	11.4
43	11.4
24	12.0
44	12.0
23	12.6
45	12.6
22	13.2	G22R,
46	13.2	A46T, A46E,
21	13.7	P21S
47	13.7
20	14.2
48	14.2
19	14.7
49	14.7

External resources

ClinVar Open gnomAD Open UniProt