TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26455	79588;79589;79590	chr2:178566769;178566768;178566767	chr2:179431496;179431495;179431494
N2AB	24814	74665;74666;74667	chr2:178566769;178566768;178566767	chr2:179431496;179431495;179431494
N2A	23887	71884;71885;71886	chr2:178566769;178566768;178566767	chr2:179431496;179431495;179431494
N2B	17390	52393;52394;52395	chr2:178566769;178566768;178566767	chr2:179431496;179431495;179431494
Novex-1	17515	52768;52769;52770	chr2:178566769;178566768;178566767	chr2:179431496;179431495;179431494
Novex-2	17582	52969;52970;52971	chr2:178566769;178566768;178566767	chr2:179431496;179431495;179431494
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-80
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.2751
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
H/L	rs1706027095	None	1.0	N	0.751	0.473	0.583959843308	gnomAD-4.0.0	2.05314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69865E-06	0	0
H/Y	None	None	0.999	N	0.606	0.522	0.330331372229	gnomAD-4.0.0	6.84394E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9953E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
H/A	0.8366	likely_pathogenic	0.8025	pathogenic	-0.459	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
H/C	0.3613	ambiguous	0.326	benign	0.504	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
H/D	0.8416	likely_pathogenic	0.8105	pathogenic	-0.347	Destabilizing	1.0	D	0.675	prob.neutral	N	0.480799306	None	None	N
H/E	0.8643	likely_pathogenic	0.8336	pathogenic	-0.262	Destabilizing	0.999	D	0.562	neutral	None	None	None	None	N
H/F	0.7911	likely_pathogenic	0.7554	pathogenic	0.582	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
H/G	0.7925	likely_pathogenic	0.762	pathogenic	-0.816	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
H/I	0.8901	likely_pathogenic	0.8679	pathogenic	0.517	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
H/K	0.5919	likely_pathogenic	0.591	pathogenic	-0.189	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
H/L	0.5956	likely_pathogenic	0.55	ambiguous	0.517	Stabilizing	1.0	D	0.751	deleterious	N	0.514593135	None	None	N
H/M	0.8789	likely_pathogenic	0.8607	pathogenic	0.452	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
H/N	0.4086	ambiguous	0.3644	ambiguous	-0.162	Destabilizing	0.999	D	0.561	neutral	N	0.448157499	None	None	N
H/P	0.9677	likely_pathogenic	0.9565	pathogenic	0.213	Stabilizing	1.0	D	0.719	prob.delet.	N	0.507804331	None	None	N
H/Q	0.5674	likely_pathogenic	0.5426	ambiguous	0.068	Stabilizing	1.0	D	0.722	prob.delet.	N	0.498276888	None	None	N
H/R	0.2352	likely_benign	0.2164	benign	-0.763	Destabilizing	1.0	D	0.706	prob.neutral	N	0.463758883	None	None	N
H/S	0.7055	likely_pathogenic	0.6677	pathogenic	-0.134	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
H/T	0.8077	likely_pathogenic	0.782	pathogenic	0.046	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
H/V	0.8257	likely_pathogenic	0.796	pathogenic	0.213	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
H/W	0.833	likely_pathogenic	0.7962	pathogenic	0.726	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
H/Y	0.4193	ambiguous	0.374	ambiguous	0.909	Stabilizing	0.999	D	0.606	neutral	N	0.47859726	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.