TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31754	95485;95486;95487	chr2:178545976;178545975;178545974	chr2:179410703;179410702;179410701
N2AB	30113	90562;90563;90564	chr2:178545976;178545975;178545974	chr2:179410703;179410702;179410701
N2A	29186	87781;87782;87783	chr2:178545976;178545975;178545974	chr2:179410703;179410702;179410701
N2B	22689	68290;68291;68292	chr2:178545976;178545975;178545974	chr2:179410703;179410702;179410701
Novex-1	22814	68665;68666;68667	chr2:178545976;178545975;178545974	chr2:179410703;179410702;179410701
Novex-2	22881	68866;68867;68868	chr2:178545976;178545975;178545974	chr2:179410703;179410702;179410701
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-119
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6217
• Predicted PPI site: I

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
N/T	None	None	0.904	N	0.435	0.409	0.243972157842	gnomAD-4.0.0	1.59121E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85814E-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
N/A	0.3184	likely_benign	0.3297	benign	-0.228	Destabilizing	0.86	D	0.464	neutral	None	None	None	None	I
N/C	0.3107	likely_benign	0.3602	ambiguous	0.144	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	I
N/D	0.4707	ambiguous	0.4968	ambiguous	0.259	Stabilizing	0.822	D	0.485	neutral	N	0.449176219	None	None	I
N/E	0.756	likely_pathogenic	0.7827	pathogenic	0.243	Stabilizing	0.86	D	0.454	neutral	None	None	None	None	I
N/F	0.6559	likely_pathogenic	0.6871	pathogenic	-0.641	Destabilizing	0.956	D	0.635	neutral	None	None	None	None	I
N/G	0.404	ambiguous	0.4017	ambiguous	-0.388	Destabilizing	0.86	D	0.475	neutral	None	None	None	None	I
N/H	0.0964	likely_benign	0.1477	benign	-0.313	Destabilizing	0.014	N	0.327	neutral	N	0.463743027	None	None	I
N/I	0.3558	ambiguous	0.3784	ambiguous	0.105	Stabilizing	0.971	D	0.649	neutral	N	0.46732205	None	None	I
N/K	0.6973	likely_pathogenic	0.7491	pathogenic	0.06	Stabilizing	0.822	D	0.426	neutral	N	0.454179394	None	None	I
N/L	0.2626	likely_benign	0.298	benign	0.105	Stabilizing	0.956	D	0.643	neutral	None	None	None	None	I
N/M	0.4607	ambiguous	0.4609	ambiguous	0.026	Stabilizing	0.998	D	0.579	neutral	None	None	None	None	I
N/P	0.7128	likely_pathogenic	0.7494	pathogenic	0.02	Stabilizing	0.993	D	0.561	neutral	None	None	None	None	I
N/Q	0.4855	ambiguous	0.53	ambiguous	-0.215	Destabilizing	0.956	D	0.467	neutral	None	None	None	None	I
N/R	0.6603	likely_pathogenic	0.7189	pathogenic	0.107	Stabilizing	0.956	D	0.466	neutral	None	None	None	None	I
N/S	0.1059	likely_benign	0.1068	benign	-0.116	Destabilizing	0.822	D	0.473	neutral	N	0.392898862	None	None	I
N/T	0.1965	likely_benign	0.1985	benign	0.002	Stabilizing	0.904	D	0.435	neutral	N	0.396960674	None	None	I
N/V	0.3437	ambiguous	0.3494	ambiguous	0.02	Stabilizing	0.978	D	0.647	neutral	None	None	None	None	I
N/W	0.8426	likely_pathogenic	0.8699	pathogenic	-0.717	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	I
N/Y	0.252	likely_benign	0.2929	benign	-0.414	Destabilizing	0.89	D	0.583	neutral	N	0.507629877	None	None	I

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.