TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20233	60922;60923;60924	chr2:178591028;178591027;178591026	chr2:179455755;179455754;179455753
N2AB	18592	55999;56000;56001	chr2:178591028;178591027;178591026	chr2:179455755;179455754;179455753
N2A	17665	53218;53219;53220	chr2:178591028;178591027;178591026	chr2:179455755;179455754;179455753
N2B	11168	33727;33728;33729	chr2:178591028;178591027;178591026	chr2:179455755;179455754;179455753
Novex-1	11293	34102;34103;34104	chr2:178591028;178591027;178591026	chr2:179455755;179455754;179455753
Novex-2	11360	34303;34304;34305	chr2:178591028;178591027;178591026	chr2:179455755;179455754;179455753
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-34
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0795
• 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
I/V	rs1434582972	-1.669	0.001	N	0.205	0.087	0.284539287134	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
I/V	rs1434582972	-1.669	0.001	N	0.205	0.087	0.284539287134	gnomAD-4.0.0	3.18377E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71935E-06	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
I/A	0.8523	likely_pathogenic	0.8791	pathogenic	-2.598	Highly Destabilizing	0.25	N	0.738	prob.delet.	None	None	None	None	N
I/C	0.8673	likely_pathogenic	0.8907	pathogenic	-1.862	Destabilizing	0.947	D	0.766	deleterious	None	None	None	None	N
I/D	0.9908	likely_pathogenic	0.9945	pathogenic	-3.524	Highly Destabilizing	0.826	D	0.853	deleterious	None	None	None	None	N
I/E	0.9851	likely_pathogenic	0.9903	pathogenic	-3.249	Highly Destabilizing	0.826	D	0.856	deleterious	None	None	None	None	N
I/F	0.4642	ambiguous	0.5047	ambiguous	-1.661	Destabilizing	0.638	D	0.753	deleterious	N	0.509688747	None	None	N
I/G	0.9748	likely_pathogenic	0.9825	pathogenic	-3.157	Highly Destabilizing	0.826	D	0.85	deleterious	None	None	None	None	N
I/H	0.9654	likely_pathogenic	0.9763	pathogenic	-2.783	Highly Destabilizing	0.982	D	0.842	deleterious	None	None	None	None	N
I/K	0.9772	likely_pathogenic	0.9846	pathogenic	-2.342	Highly Destabilizing	0.826	D	0.855	deleterious	None	None	None	None	N
I/L	0.2748	likely_benign	0.2758	benign	-0.948	Destabilizing	0.043	N	0.408	neutral	N	0.472781011	None	None	N
I/M	0.3183	likely_benign	0.3355	benign	-0.845	Destabilizing	0.638	D	0.721	prob.delet.	N	0.473209344	None	None	N
I/N	0.8618	likely_pathogenic	0.9076	pathogenic	-2.918	Highly Destabilizing	0.916	D	0.854	deleterious	N	0.491655994	None	None	N
I/P	0.9776	likely_pathogenic	0.9851	pathogenic	-1.485	Destabilizing	0.935	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9712	likely_pathogenic	0.9793	pathogenic	-2.696	Highly Destabilizing	0.935	D	0.869	deleterious	None	None	None	None	N
I/R	0.9663	likely_pathogenic	0.977	pathogenic	-2.135	Highly Destabilizing	0.826	D	0.861	deleterious	None	None	None	None	N
I/S	0.8597	likely_pathogenic	0.9026	pathogenic	-3.474	Highly Destabilizing	0.638	D	0.819	deleterious	N	0.491149015	None	None	N
I/T	0.8587	likely_pathogenic	0.8874	pathogenic	-3.05	Highly Destabilizing	0.201	N	0.763	deleterious	N	0.470829488	None	None	N
I/V	0.0883	likely_benign	0.0897	benign	-1.485	Destabilizing	0.001	N	0.205	neutral	N	0.364653468	None	None	N
I/W	0.9836	likely_pathogenic	0.9878	pathogenic	-2.165	Highly Destabilizing	0.982	D	0.818	deleterious	None	None	None	None	N
I/Y	0.8952	likely_pathogenic	0.9222	pathogenic	-1.83	Destabilizing	0.826	D	0.78	deleterious	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.