TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32502	97729;97730;97731	chr2:178541573;178541572;178541571	chr2:179406300;179406299;179406298
N2AB	30861	92806;92807;92808	chr2:178541573;178541572;178541571	chr2:179406300;179406299;179406298
N2A	29934	90025;90026;90027	chr2:178541573;178541572;178541571	chr2:179406300;179406299;179406298
N2B	23437	70534;70535;70536	chr2:178541573;178541572;178541571	chr2:179406300;179406299;179406298
Novex-1	23562	70909;70910;70911	chr2:178541573;178541572;178541571	chr2:179406300;179406299;179406298
Novex-2	23629	71110;71111;71112	chr2:178541573;178541572;178541571	chr2:179406300;179406299;179406298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-125
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3039
• 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
P/L	None	None	0.026	N	0.604	0.358	0.543691374674	gnomAD-4.0.0	1.37501E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80591E-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
P/A	0.0719	likely_benign	0.0629	benign	-1.355	Destabilizing	0.103	N	0.481	neutral	N	0.466124397	None	None	N
P/C	0.432	ambiguous	0.3651	ambiguous	-0.876	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
P/D	0.7478	likely_pathogenic	0.7284	pathogenic	-1.55	Destabilizing	0.976	D	0.755	deleterious	None	None	None	None	N
P/E	0.3847	ambiguous	0.3434	ambiguous	-1.609	Destabilizing	0.976	D	0.756	deleterious	None	None	None	None	N
P/F	0.5006	ambiguous	0.4289	ambiguous	-1.281	Destabilizing	0.976	D	0.837	deleterious	None	None	None	None	N
P/G	0.438	ambiguous	0.3987	ambiguous	-1.607	Destabilizing	0.851	D	0.771	deleterious	None	None	None	None	N
P/H	0.2823	likely_benign	0.2532	benign	-1.182	Destabilizing	0.999	D	0.809	deleterious	N	0.513532458	None	None	N
P/I	0.3168	likely_benign	0.2501	benign	-0.778	Destabilizing	0.952	D	0.813	deleterious	None	None	None	None	N
P/K	0.3976	ambiguous	0.3693	ambiguous	-1.07	Destabilizing	0.976	D	0.743	deleterious	None	None	None	None	N
P/L	0.1809	likely_benign	0.1534	benign	-0.778	Destabilizing	0.026	N	0.604	neutral	N	0.513278968	None	None	N
P/M	0.3262	likely_benign	0.264	benign	-0.511	Destabilizing	0.993	D	0.821	deleterious	None	None	None	None	N
P/N	0.5257	ambiguous	0.4741	ambiguous	-0.785	Destabilizing	0.976	D	0.811	deleterious	None	None	None	None	N
P/Q	0.1857	likely_benign	0.1574	benign	-1.077	Destabilizing	0.988	D	0.751	deleterious	None	None	None	None	N
P/R	0.2512	likely_benign	0.2322	benign	-0.481	Destabilizing	0.984	D	0.812	deleterious	N	0.50361773	None	None	N
P/S	0.1428	likely_benign	0.125	benign	-1.188	Destabilizing	0.437	N	0.511	neutral	N	0.498530391	None	None	N
P/T	0.163	likely_benign	0.1358	benign	-1.154	Destabilizing	0.811	D	0.732	prob.delet.	N	0.501415684	None	None	N
P/V	0.2344	likely_benign	0.1808	benign	-0.936	Destabilizing	0.851	D	0.78	deleterious	None	None	None	None	N
P/W	0.7512	likely_pathogenic	0.7029	pathogenic	-1.403	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
P/Y	0.5398	ambiguous	0.4786	ambiguous	-1.129	Destabilizing	0.988	D	0.85	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.