TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32251	96976;96977;96978	chr2:178543222;178543221;178543220	chr2:179407949;179407948;179407947
N2AB	30610	92053;92054;92055	chr2:178543222;178543221;178543220	chr2:179407949;179407948;179407947
N2A	29683	89272;89273;89274	chr2:178543222;178543221;178543220	chr2:179407949;179407948;179407947
N2B	23186	69781;69782;69783	chr2:178543222;178543221;178543220	chr2:179407949;179407948;179407947
Novex-1	23311	70156;70157;70158	chr2:178543222;178543221;178543220	chr2:179407949;179407948;179407947
Novex-2	23378	70357;70358;70359	chr2:178543222;178543221;178543220	chr2:179407949;179407948;179407947
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-123
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.2789
• 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
K/N	rs1327194086	-0.227	0.134	N	0.19	0.109	0.168933306366	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.87E-06	0
K/N	rs1327194086	-0.227	0.134	N	0.19	0.109	0.168933306366	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1327194086	-0.227	0.134	N	0.19	0.109	0.168933306366	gnomAD-4.0.0	2.56275E-06	None	None	None	None	N	None	3.38742E-05	0	None	0	0	None	0	0	0	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
K/A	0.374	ambiguous	0.3225	benign	-0.159	Destabilizing	0.863	D	0.443	neutral	None	None	None	None	N
K/C	0.7346	likely_pathogenic	0.7158	pathogenic	-0.405	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
K/D	0.6062	likely_pathogenic	0.5674	pathogenic	0.134	Stabilizing	0.884	D	0.459	neutral	None	None	None	None	N
K/E	0.2216	likely_benign	0.1908	benign	0.2	Stabilizing	0.92	D	0.414	neutral	N	0.467919482	None	None	N
K/F	0.8783	likely_pathogenic	0.8317	pathogenic	-0.012	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
K/G	0.5693	likely_pathogenic	0.5167	ambiguous	-0.458	Destabilizing	0.939	D	0.491	neutral	None	None	None	None	N
K/H	0.3299	likely_benign	0.3144	benign	-0.696	Destabilizing	0.991	D	0.537	neutral	None	None	None	None	N
K/I	0.4738	ambiguous	0.4128	ambiguous	0.578	Stabilizing	0.884	D	0.549	neutral	None	None	None	None	N
K/L	0.4224	ambiguous	0.3671	ambiguous	0.578	Stabilizing	0.759	D	0.475	neutral	None	None	None	None	N
K/M	0.2797	likely_benign	0.2377	benign	0.251	Stabilizing	0.988	D	0.536	neutral	N	0.499050466	None	None	N
K/N	0.4194	ambiguous	0.3723	ambiguous	-0.125	Destabilizing	0.134	N	0.19	neutral	N	0.506763085	None	None	N
K/P	0.4643	ambiguous	0.4407	ambiguous	0.363	Stabilizing	0.997	D	0.559	neutral	None	None	None	None	N
K/Q	0.162	likely_benign	0.1507	benign	-0.215	Destabilizing	0.988	D	0.499	neutral	N	0.476960253	None	None	N
K/R	0.0932	likely_benign	0.0886	benign	-0.327	Destabilizing	0.959	D	0.393	neutral	N	0.457259772	None	None	N
K/S	0.4709	ambiguous	0.4206	ambiguous	-0.694	Destabilizing	0.759	D	0.411	neutral	None	None	None	None	N
K/T	0.1806	likely_benign	0.1513	benign	-0.446	Destabilizing	0.061	N	0.233	neutral	N	0.426822221	None	None	N
K/V	0.372	ambiguous	0.3279	benign	0.363	Stabilizing	0.17	N	0.339	neutral	None	None	None	None	N
K/W	0.8351	likely_pathogenic	0.8046	pathogenic	0.043	Stabilizing	0.999	D	0.586	neutral	None	None	None	None	N
K/Y	0.7182	likely_pathogenic	0.6705	pathogenic	0.349	Stabilizing	0.997	D	0.579	neutral	None	None	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.