Variant detail

KCNH2I82dup

c.244dup · residue 82 · I → dup

Technical Plain language

HGVS annotation

ClinVar-style identity and transcript context

ClinVar-style HGVS

NM_000238.4(KCNH2):c.244dup (I82dup)

HGVSc

c.244dup

cDNA change

c.244dup

RefSeq transcript

NM_000238.4

Ensembl transcript

ENST00000262186.10

Protein HGVS

I82dup

Genomic coordinate

Chr7 150671862

ClinVar annotation

Not annotated in local ClinVar field

LQT2 penetrance Low risk

0% CI pending

0%20%50%100%

Limited evidence · n=1 1 observed LQT2 carriers · NA hypothetical affected and NA hypothetical unaffected

One-sentence summary

Roughly fewer than 1 in 100 people who carry I82dup are estimated to eventually be diagnosed with Long QT type 2 — low risk penetrance, based on 1 carriers reported so far.

Structure: Hotspot. Functional evidence: MAVE not available.

Executive summary

Sources used for interpretation

The LQT2 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 estimate0% · Low risk

Model inputHypothetical observationsNA affected · NA unaffected

ObservedObserved carriers (literature + cohorts)1 · Limited evidence

ObservedPopulation observations (gnomAD v4)0 alleles

PredictedIn silico predictorsREVEL · PolyPhen-2 · PROVEAN · BLAST-PSSM

ObservedFunctional / MAVE dataNot characterized · 0 studies

PredictedStructural contextHotspot

ExternalAutomated ACMG reviewNot a classification

ExternalExternal databasesClinVar · gnomAD · UniProt

Evidence

Carriers observed

1 LQT2 · 0 unaffected · 0 gnomAD

Model prior: NA hypothetical affected · NA hypothetical unaffected

Limited evidence

Functional data

Not characterized

MAVE not available · 0 published functional studies

Predictors and density

REVEL—range 0-1

LQT2 densityHotspot region0.696range 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

Functional studies or MAVE support effect

PM1review

Hotspot or high LQT2 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	LQT2 / affected	Unaffected / ambiguous	Other observations	Variant context
PMID 23098067 Year 2012 · clinical carrier record	1	1 LQT2	0 unaffected / ambiguous	Not separately annotated	Variant I82dup Curated carrier-count row
gnomAD population observations (v4)	0	0 LQT2	0	Population observations; not known affected cases.	gnomAD v4 allele count.
Combined literature, cohort, and gnomAD	1	1 LQT2	0	Combined totals used in the penetrance estimate.	Curated carrier totals for this variant.
Hypothetical observations from model prior (not observed patients)	NA	NA hypothetical LQT2 affected	NA 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 NA hypothetical affected and NA 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
82	0.0	I82Del, I82dup, I82Ins, I82T,
83	4.5	A83P, A83fsX,
79	5.1	A79T, A79S, A79Del, A79fsX,
81	5.4	Q81E, Q81X, Q81P, Q81H, Q81H,
80	5.5	A80P,
85	5.9	A85P, A85V,
94	6.5	V94L, V94L, V94A,
65	6.6	T65P,
78	6.9	A78T, A78P,
84	6.9
86	6.9	L86R,
110	7.3	V110A,
112	7.8	V112M,
92	8.0	R92C, R92L,
64	8.3	C64R, C64Y,
96	8.6	I96V, I96T,
66	9.2	C66R, C66G, C66Y,
77	9.3	R77S,
127	9.4
87	10.1	L87P,
70	10.3	H70R, H70Q, H70Q,
76	10.4
111	10.6	D111V,
125	10.7
98	10.7
95	10.9	E95K, E95G,
90	10.9	E90K,
93	11.2	K93X, K93R,
88	11.2
67	11.2
109	11.3	L109X, L109Q, L109P,
75	11.5	Q75X,
63	11.7	P63H,
129	11.7	F129C,
69	11.8	L69Del, L69P,
74	11.9	T74fsX, T74M,
108	12.0	C108Y,
89	12.0	A89G, A89V,
39	12.0	C39R, C39X,
113	12.2	V113Del,
97	12.2
91	12.3
114	12.5	P114S,
30	12.8	I30Del, I30T,
126	12.9
128	13.0	N128S,
32	13.1	A32T
68	13.8	F68L, F68V, F68L, F68L,
71	14.2	G71R, G71R, G71W, G71E,
38	14.2
41	14.8	V41A,
40	14.8
107	14.9	L107P,

External resources

ClinVar Open gnomAD Open UniProt