Variant detail

KCNQ1F339del

c.1017del · residue 339 · Chr11 2604760

Technical Plain language

HGVS annotation

ClinVar-style identity and transcript context

ClinVar-style HGVS

NM_000218.3(KCNQ1):c.1017del (F339del)

HGVSc

c.1017del

cDNA change

c.1017del

RefSeq transcript

NM_000218.3

Ensembl transcript

ENST00000155840.12

Protein HGVS

F339del

Genomic coordinate

Chr11 2604760

ClinVar annotation

Not annotated in local ClinVar field

LQT1 penetrance High risk

79% 90% credible interval 65-91%

0%20%50%100%

Emerging evidence · n=16 13 observed LQT1 carriers · 7.55 hypothetical affected and 2.45 hypothetical unaffected

One-sentence summary

Roughly 8 in 10 people who carry F339del are estimated to eventually be diagnosed with Long QT type 1 — high risk penetrance, based on 16 carriers reported so far.

Structure: NA. 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 estimate79% · High risk

Model inputHypothetical observations7.55 affected · 2.45 unaffected

ObservedObserved carriers (literature + cohorts)16 · Emerging evidence

ObservedPopulation observations (gnomAD v4)0 alleles

PredictedIn silico predictorsREVEL · PolyPhen-2 · PROVEAN

ObservedFunctional classNA

PredictedStructural contextNA

ExternalAutomated ACMG reviewNot a classification

ExternalExternal databasesClinVar · gnomAD · UniProt

Evidence

Carriers observed

13 LQT1 · 3 unaffected/other · 0 gnomAD

Model prior: 7.55 hypothetical affected · 2.45 hypothetical unaffected

Emerging evidence

Functional data

0 published functional studies

Predictors and density

REVEL—range 0-1

LQT1 densityHotspot region0.766range 0-1

PolyPhen-2—range 0-1

PROVEAN—cutoff <= -2.5

BLAST-PSSM—lower = less tolerated

Overall0/5

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
PMID 26715165 Year 2016 · clinical carrier record	1	1 LQT1	0 asymptomatic	Not separately annotated	Variant F339del Curated carrier-count row
PMID 24606995 Year 2014 · clinical carrier record	1	1 LQT1	0 asymptomatic	Not separately annotated	Variant F339del Curated carrier-count row
PMID 12877697 Year 2003 · clinical carrier record	4	0 LQT1	4 asymptomatic	Not separately annotated	Variant F339del Curated carrier-count row
PMID 9702906 Year 1998 · clinical carrier record	10	10 LQT1	0 asymptomatic	Not separately annotated	Variant F339del Curated carrier-count row
gnomAD population observations (v4)	0	0 LQT1	0	Population observations; not known affected cases.	gnomAD v4 allele count.
Combined literature, cohort, and gnomAD	16	13 LQT1	3	Combined totals used in the penetrance estimate.	Curated carrier totals for this variant.
Hypothetical observations from model prior (not observed patients)	10	7.55 hypothetical LQT1 affected	2.45 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 7.55 hypothetical affected and 2.45 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
271	9.6
250	11.5	L250H, L250P,
266	11.7	L266P,
247	11.8	T247I,
262	11.8	L262P, L262R, L262V,
248	11.9	W248C, W248C, W248R, W248R
276	12.5	S276del,
255	12.7
274	12.8	I274V,
275	13.1	F275del,
270	14.0	F270S,
254	14.3	V254M, V254L, V254L,
252	14.4	G252R,
263	14.4
339	14.5	F339del, F339S,
341	14.7	A341V, A341E,
258	14.8	H258P, H258N, H258R, H258Y,
334	15.0	V334A,

External resources

ClinVar Open gnomAD Open UniProt