TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33745	101458;101459;101460	chr2:178535382;178535381;178535380	chr2:179400109;179400108;179400107
N2AB	32104	96535;96536;96537	chr2:178535382;178535381;178535380	chr2:179400109;179400108;179400107
N2A	31177	93754;93755;93756	chr2:178535382;178535381;178535380	chr2:179400109;179400108;179400107
N2B	24680	74263;74264;74265	chr2:178535382;178535381;178535380	chr2:179400109;179400108;179400107
Novex-1	24805	74638;74639;74640	chr2:178535382;178535381;178535380	chr2:179400109;179400108;179400107
Novex-2	24872	74839;74840;74841	chr2:178535382;178535381;178535380	chr2:179400109;179400108;179400107
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: Fn3-132
• Domain position: 57
• Structural Position: 89
• Q(SASA): 0.2135
• 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/R	None	None	0.999	N	0.622	0.401	0.591849201417	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1252	likely_benign	0.1732	benign	-0.867	Destabilizing	0.341	N	0.37	neutral	N	0.515577356	None	None	N
T/C	0.374	ambiguous	0.4144	ambiguous	-0.418	Destabilizing	0.053	N	0.311	neutral	None	None	None	None	N
T/D	0.6755	likely_pathogenic	0.8077	pathogenic	-0.699	Destabilizing	0.991	D	0.575	neutral	None	None	None	None	N
T/E	0.5388	ambiguous	0.6796	pathogenic	-0.555	Destabilizing	0.997	D	0.577	neutral	None	None	None	None	N
T/F	0.6799	likely_pathogenic	0.8339	pathogenic	-0.628	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
T/G	0.3237	likely_benign	0.4461	ambiguous	-1.246	Destabilizing	0.989	D	0.586	neutral	None	None	None	None	N
T/H	0.4716	ambiguous	0.6588	pathogenic	-1.381	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
T/I	0.5163	ambiguous	0.6112	pathogenic	0.106	Stabilizing	0.992	D	0.562	neutral	N	0.47372955	None	None	N
T/K	0.2094	likely_benign	0.3386	benign	-0.428	Destabilizing	0.997	D	0.576	neutral	N	0.482427575	None	None	N
T/L	0.1665	likely_benign	0.1971	benign	0.106	Stabilizing	0.96	D	0.475	neutral	None	None	None	None	N
T/M	0.1276	likely_benign	0.1582	benign	0.088	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	N
T/N	0.1411	likely_benign	0.2346	benign	-0.845	Destabilizing	0.991	D	0.491	neutral	None	None	None	None	N
T/P	0.1332	likely_benign	0.1882	benign	-0.186	Destabilizing	0.988	D	0.61	neutral	N	0.488950903	None	None	N
T/Q	0.2745	likely_benign	0.3997	ambiguous	-0.699	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	N
T/R	0.2222	likely_benign	0.3791	ambiguous	-0.527	Destabilizing	0.999	D	0.622	neutral	N	0.48042742	None	None	N
T/S	0.1946	likely_benign	0.3016	benign	-1.107	Destabilizing	0.718	D	0.439	neutral	N	0.517886943	None	None	N
T/V	0.3449	ambiguous	0.4122	ambiguous	-0.186	Destabilizing	0.945	D	0.397	neutral	None	None	None	None	N
T/W	0.8968	likely_pathogenic	0.9563	pathogenic	-0.756	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
T/Y	0.6348	likely_pathogenic	0.8148	pathogenic	-0.392	Destabilizing	0.999	D	0.689	prob.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.