Variant detail

SCN5Ac.2582_2583delTT

c.2582_2583delTT · residue 861 · NA → NA
Technical Plain language
HGVS annotation

ClinVar-style identity and transcript context

ClinVar-style HGVS
NM_000335.5(SCN5A):c.2582_2583delTT (c.2582_2583delTT)
HGVSc
c.2582_2583delTT
cDNA change
c.2582_2583delTT
RefSeq transcript
NM_000335.5
Ensembl transcript
ENST00000333535.9
Protein HGVS
c.2582_2583delTT
Genomic coordinate
Not available in current dataset
ClinVar annotation
Not annotated in local ClinVar field
BrS1 penetrance High risk
70% 90% credible interval 53–85%
0%20%50%100%

Emerging evidence · n=11 11 observed BrS1 carriers · 3.66 hypothetical affected and 6.34 hypothetical unaffected

LQT3 penetrance Low risk
10% 90% credible interval 1–24%
0%20%50%100%

Emerging evidence · n=11 0 observed LQT3 carriers · 1.53 hypothetical affected and 3.47 hypothetical unaffected

One-sentence summary

Roughly 7 in 10 people who carry c.2582_2583delTT are estimated to eventually be diagnosed with Brugada syndrome — high penetrance, though evidence is limited (11 carriers). The residue lies in a Hotspot region for BrS1 and a Mild_Hotspot region for LQT3.

Executive summary

Sources used for interpretation

The BrS1 and LQT3 penetrance estimates combine observed carrier counts with phenotype-specific feature-based model starting points. 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 estimatesBrS1 70% · LQT3 10%
Model inputHypothetical observationsBrS1 3.66/6.34 · LQT3 1.53/3.47
ObservedObserved carriers (literature + cohorts)11 · Emerging evidence
ObservedPopulation observations (gnomAD v4)0 alleles
PredictedIn silico predictorsREVEL · PolyPhen-2 · PROVEAN · BLAST-PSSM
ObservedFunctional / electrophysiologyNA
PredictedStructural contextHotspot
ExternalClinVar classificationNot annotated
ExternalAutomated ACMG reviewNot a classification
ExternalExternal databasesClinVar · gnomAD · UniProt

Evidence

Carriers observed
11
11 BrS1 · 0 LQT3 · 0 unaffected
Model prior: BrS1 3.66 hypothetical affected / 6.34 hypothetical unaffected; LQT3 1.53 hypothetical affected / 3.47 hypothetical unaffected
Emerging evidence
Functional data
NA
8 published electrophysiology studies
Predictors and density
REVEL —range 0-1
PolyPhen-2 NArange 0-1
BrS1 density Hotspot region0.513range 0-1
LQT3 density Sparse region0.392range 0-1
PROVEAN NAcutoff <= -2.5
BLAST-PSSM NAlower = less tolerated
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
PS3met · strong
Functional studies show damaging effect
PM1review
Hotspot or high BrS1/LQT3 density
PM2met · moderate
Absent / extremely rare in population databases
PP3not met
Multiple computational predictors support deleterious
BS1not met
Allele frequency too high for disorder
BP4met · supporting
Computational predictors suggest no impact

Reported carrier data

Paper / cohort Carriers LQT3 / BrS1 Unaffected Other observations Variant context
Year 2009 · clinical carrier record
1 0 LQT3
1 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2009 · clinical carrier record
1 0 LQT3
1 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2011 · clinical carrier record
7 0 LQT3
7 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2012 · clinical carrier record
3 0 LQT3
3 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2016 · clinical carrier record
1 0 LQT3
1 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2016 · clinical carrier record
2 0 LQT3
2 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2010 · clinical carrier record
11 0 LQT3
11 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue 861
Curated carrier-count row
Year 2018 · clinical carrier record
1 0 LQT3
1 BrS1 		0 Not separately annotated
Variant c.2582_2583delTT
Residue *
Curated carrier-count row
gnomAD population observations (v4) 0 0 LQT3
0 BrS1		 0 Population observations; not known affected cases. gnomAD v4 allele count.
Hypothetical observations from model prior (not observed patients) 5 LQT3 prior;
10 BrS1 prior		 1.53 hypothetical LQT3 affected;
3.66 hypothetical BrS1 affected		 3.47 hypothetical LQT3 unaffected;
6.34 hypothetical BrS1 unaffected		 Phenotype-specific feature-based pseudo-counts added before observed carriers. Model input; not literature or gnomAD evidence.
Combined literature, cohort, and gnomAD 11 0 LQT3
11 BrS1		 0 Combined totals used in the dual penetrance estimates. Curated carrier totals for this variant.

Model starting point. The BrS1 model starts with 3.66 hypothetical affected and 6.34 hypothetical unaffected observations; the LQT3 model starts with 1.53 hypothetical affected and 3.47 hypothetical unaffected observations. Each then updates that starting point with the real carrier counts above. As observed carrier counts grow, these feature-based starting points have less influence.

Functional studies · researcher detail
PMIDYearCellPeak (%WT)V½ act (mV)V½ inact (mV)Late (%WT)
19251209 2009 ————
19029124 2009 ————
21273195 2011 ————
22885917 2012 ————
26921764 2016 ————
26941339 2016 ————
20129283 2010 ————
29759671 2018 ————
Structural neighbours · researcher detail

Residues within 15 Å of c.2582_2583delTT; observed variants link to their detail pages.

NeighbourDistance (Å)Observed variants
89111.4 I891N, I891T,
88010.9
88814.8
22313.9 V223L,
8567.6 V856L, V856L,
89010.5 I890T,
90115.0 E901K, S901L,
9198.8
8625.2
86711.5 E867K, E867Q, E867X,
8597.6
89413.5 I894M,
8638.4
90413.9 W904X,
88710.0
8646.7
88613.2 H886P, H886Q, H886Q,
21610.6 S216X, S216L,
22112.3
9098.6
85213.6
8549.8 c.2559delT,
87614.1
8574.7 G857D,
86812.7 c.2602delC, L868X,
90210.4
88210.6
8815.9
92113.2
92213.1 V922I
8603.8 p.L860fsx89,
9119.7 G911E,
92013.7
88914.9
8588.0 M858L, M858L,
21711.5
9188.2
85510.3
91711.3 L917V, L917R,
8657.4
9138.8
91611.2
91211.8 Q912R,
88413.6
9066.2
86611.7 S866P, S866L,
9106.5 S910L,
90310.8 p.M903CfsX29,
85311.4
21912.7 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
87713.2
87914.7 W879R, W879R,
88312.8
90511.0
9156.1 C915R,
21513.0 p.L215CfsX10,
85014.9 V850M, c.2549_2550insTG,
90811.9
9146.6
8610.0 p.F861WfsX90, c.2582_2583delTT,
2209.4 T220I,
9079.8
View this variant elsewhere
ClinVar → gnomAD → UniProt →