TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15182	45769;45770;45771	chr2:178621174;178621173;178621172	chr2:179485901;179485900;179485899
N2AB	13541	40846;40847;40848	chr2:178621174;178621173;178621172	chr2:179485901;179485900;179485899
N2A	12614	38065;38066;38067	chr2:178621174;178621173;178621172	chr2:179485901;179485900;179485899
N2B	6117	18574;18575;18576	chr2:178621174;178621173;178621172	chr2:179485901;179485900;179485899
Novex-1	6242	18949;18950;18951	chr2:178621174;178621173;178621172	chr2:179485901;179485900;179485899
Novex-2	6309	19150;19151;19152	chr2:178621174;178621173;178621172	chr2:179485901;179485900;179485899
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-103
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.2319
• 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
T/A	None	None	0.454	N	0.357	0.158	0.238096912614	gnomAD-4.0.0	1.59362E-06	None	None	None	None	N	None	0	0	None	0	2.78847E-05	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
T/A	0.085	likely_benign	0.0924	benign	-0.811	Destabilizing	0.454	N	0.357	neutral	N	0.50859011	None	None	N
T/C	0.4031	ambiguous	0.4177	ambiguous	-0.569	Destabilizing	0.998	D	0.385	neutral	None	None	None	None	N
T/D	0.3319	likely_benign	0.3535	ambiguous	-0.646	Destabilizing	0.728	D	0.371	neutral	None	None	None	None	N
T/E	0.2727	likely_benign	0.2953	benign	-0.644	Destabilizing	0.029	N	0.154	neutral	None	None	None	None	N
T/F	0.2486	likely_benign	0.32	benign	-0.892	Destabilizing	0.949	D	0.447	neutral	None	None	None	None	N
T/G	0.2155	likely_benign	0.1848	benign	-1.074	Destabilizing	0.842	D	0.405	neutral	None	None	None	None	N
T/H	0.2111	likely_benign	0.2552	benign	-1.365	Destabilizing	0.991	D	0.423	neutral	None	None	None	None	N
T/I	0.1852	likely_benign	0.2498	benign	-0.201	Destabilizing	0.669	D	0.357	neutral	D	0.569612986	None	None	N
T/K	0.1376	likely_benign	0.1525	benign	-0.847	Destabilizing	0.012	N	0.198	neutral	N	0.505899797	None	None	N
T/L	0.0977	likely_benign	0.1171	benign	-0.201	Destabilizing	0.525	D	0.385	neutral	None	None	None	None	N
T/M	0.0999	likely_benign	0.1257	benign	0.17	Stabilizing	0.974	D	0.367	neutral	None	None	None	None	N
T/N	0.1037	likely_benign	0.1084	benign	-0.856	Destabilizing	0.842	D	0.371	neutral	None	None	None	None	N
T/P	0.3802	ambiguous	0.4438	ambiguous	-0.372	Destabilizing	0.966	D	0.346	neutral	D	0.603753629	None	None	N
T/Q	0.1768	likely_benign	0.192	benign	-1.062	Destabilizing	0.842	D	0.356	neutral	None	None	None	None	N
T/R	0.1324	likely_benign	0.1551	benign	-0.553	Destabilizing	0.669	D	0.371	neutral	N	0.509516008	None	None	N
T/S	0.0886	likely_benign	0.0844	benign	-1.089	Destabilizing	0.625	D	0.383	neutral	N	0.507216879	None	None	N
T/V	0.1363	likely_benign	0.1613	benign	-0.372	Destabilizing	0.016	N	0.183	neutral	None	None	None	None	N
T/W	0.6748	likely_pathogenic	0.767	pathogenic	-0.832	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	N
T/Y	0.3252	likely_benign	0.4067	ambiguous	-0.593	Destabilizing	0.974	D	0.447	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.