TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17350	52273;52274;52275	chr2:178609262;178609261;178609260	chr2:179473989;179473988;179473987
N2AB	15709	47350;47351;47352	chr2:178609262;178609261;178609260	chr2:179473989;179473988;179473987
N2A	14782	44569;44570;44571	chr2:178609262;178609261;178609260	chr2:179473989;179473988;179473987
N2B	8285	25078;25079;25080	chr2:178609262;178609261;178609260	chr2:179473989;179473988;179473987
Novex-1	8410	25453;25454;25455	chr2:178609262;178609261;178609260	chr2:179473989;179473988;179473987
Novex-2	8477	25654;25655;25656	chr2:178609262;178609261;178609260	chr2:179473989;179473988;179473987
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-112
• Domain position: 100
• Structural Position: 157
• Q(SASA): 0.2476
• 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/R	rs545725664	-1.141	0.026	N	0.433	0.111	0.369682402691	gnomAD-2.1.1	5.25E-05	None	None	None	None	N	None	0	4.19E-05	None	0	0	None	0	None	0	9.79E-05	0
K/R	rs545725664	-1.141	0.026	N	0.433	0.111	0.369682402691	gnomAD-4.0.0	1.2239E-05	None	None	None	None	N	None	0	3.04971E-05	None	0	0	None	0	0	1.48099E-05	0	0
K/T	None	None	0.984	N	0.711	0.386	0.392855499163	gnomAD-4.0.0	7.19939E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.74984E-05

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	0.4454	ambiguous	0.4079	ambiguous	-0.912	Destabilizing	0.919	D	0.723	prob.delet.	None	None	None	None	N
K/C	0.6605	likely_pathogenic	0.659	pathogenic	-1.158	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/D	0.8363	likely_pathogenic	0.7933	pathogenic	-1.088	Destabilizing	0.988	D	0.703	prob.neutral	None	None	None	None	N
K/E	0.245	likely_benign	0.2191	benign	-0.885	Destabilizing	0.811	D	0.745	deleterious	N	0.498773612	None	None	N
K/F	0.8273	likely_pathogenic	0.8037	pathogenic	-0.208	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
K/G	0.7712	likely_pathogenic	0.7278	pathogenic	-1.363	Destabilizing	0.959	D	0.718	prob.delet.	None	None	None	None	N
K/H	0.3115	likely_benign	0.2988	benign	-1.643	Destabilizing	0.997	D	0.727	prob.delet.	None	None	None	None	N
K/I	0.2985	likely_benign	0.2758	benign	0.315	Stabilizing	0.984	D	0.801	deleterious	N	0.503046068	None	None	N
K/L	0.3664	ambiguous	0.3373	benign	0.315	Stabilizing	0.919	D	0.718	prob.delet.	None	None	None	None	N
K/M	0.1898	likely_benign	0.1778	benign	0.014	Stabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
K/N	0.6031	likely_pathogenic	0.5377	ambiguous	-1.382	Destabilizing	0.968	D	0.677	prob.neutral	N	0.487088816	None	None	N
K/P	0.9891	likely_pathogenic	0.9844	pathogenic	-0.066	Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
K/Q	0.1403	likely_benign	0.1356	benign	-1.229	Destabilizing	0.437	N	0.449	neutral	N	0.510297328	None	None	N
K/R	0.0934	likely_benign	0.0934	benign	-1.215	Destabilizing	0.026	N	0.433	neutral	N	0.485036311	None	None	N
K/S	0.4972	ambiguous	0.4487	ambiguous	-1.931	Destabilizing	0.919	D	0.687	prob.neutral	None	None	None	None	N
K/T	0.1355	likely_benign	0.1222	benign	-1.498	Destabilizing	0.984	D	0.711	prob.delet.	N	0.468893422	None	None	N
K/V	0.2777	likely_benign	0.2594	benign	-0.066	Destabilizing	0.988	D	0.74	deleterious	None	None	None	None	N
K/W	0.8017	likely_pathogenic	0.7996	pathogenic	-0.208	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
K/Y	0.6796	likely_pathogenic	0.6561	pathogenic	0.112	Stabilizing	0.996	D	0.777	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.