TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32477	97654;97655;97656	chr2:178542327;178542326;178542325	chr2:179407054;179407053;179407052
N2AB	30836	92731;92732;92733	chr2:178542327;178542326;178542325	chr2:179407054;179407053;179407052
N2A	29909	89950;89951;89952	chr2:178542327;178542326;178542325	chr2:179407054;179407053;179407052
N2B	23412	70459;70460;70461	chr2:178542327;178542326;178542325	chr2:179407054;179407053;179407052
Novex-1	23537	70834;70835;70836	chr2:178542327;178542326;178542325	chr2:179407054;179407053;179407052
Novex-2	23604	71035;71036;71037	chr2:178542327;178542326;178542325	chr2:179407054;179407053;179407052
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: Fn3-124
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1962
• 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/I	None	None	0.921	N	0.525	0.323	0.403609169532	gnomAD-4.0.0	2.05347E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69898E-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
T/A	0.1115	likely_benign	0.0989	benign	-1.227	Destabilizing	0.906	D	0.49	neutral	N	0.449061576	None	None	N
T/C	0.3719	ambiguous	0.3634	ambiguous	-1.333	Destabilizing	1.0	D	0.556	neutral	None	None	None	None	N
T/D	0.8953	likely_pathogenic	0.8745	pathogenic	-1.768	Destabilizing	0.969	D	0.548	neutral	None	None	None	None	N
T/E	0.618	likely_pathogenic	0.6015	pathogenic	-1.657	Destabilizing	0.939	D	0.549	neutral	None	None	None	None	N
T/F	0.5899	likely_pathogenic	0.5155	ambiguous	-1.369	Destabilizing	0.991	D	0.571	neutral	None	None	None	None	N
T/G	0.4143	ambiguous	0.3655	ambiguous	-1.502	Destabilizing	0.984	D	0.525	neutral	None	None	None	None	N
T/H	0.5362	ambiguous	0.5019	ambiguous	-1.673	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
T/I	0.3298	likely_benign	0.2925	benign	-0.546	Destabilizing	0.921	D	0.525	neutral	N	0.41800795	None	None	N
T/K	0.3926	ambiguous	0.3957	ambiguous	-0.69	Destabilizing	0.921	D	0.535	neutral	N	0.432073326	None	None	N
T/L	0.2178	likely_benign	0.1885	benign	-0.546	Destabilizing	0.864	D	0.465	neutral	None	None	None	None	N
T/M	0.13	likely_benign	0.1117	benign	-0.479	Destabilizing	0.546	D	0.323	neutral	None	None	None	None	N
T/N	0.3559	ambiguous	0.3099	benign	-1.173	Destabilizing	0.984	D	0.54	neutral	None	None	None	None	N
T/P	0.7313	likely_pathogenic	0.7382	pathogenic	-0.745	Destabilizing	0.998	D	0.571	neutral	N	0.471951442	None	None	N
T/Q	0.3164	likely_benign	0.3147	benign	-1.282	Destabilizing	0.546	D	0.341	neutral	None	None	None	None	N
T/R	0.3509	ambiguous	0.333	benign	-0.578	Destabilizing	0.988	D	0.557	neutral	N	0.445770555	None	None	N
T/S	0.2044	likely_benign	0.1787	benign	-1.345	Destabilizing	0.906	D	0.543	neutral	N	0.467263335	None	None	N
T/V	0.1815	likely_benign	0.1752	benign	-0.745	Destabilizing	0.864	D	0.515	neutral	None	None	None	None	N
T/W	0.8508	likely_pathogenic	0.8091	pathogenic	-1.407	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
T/Y	0.5933	likely_pathogenic	0.5379	ambiguous	-1.035	Destabilizing	0.999	D	0.561	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.