TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3348	10267;10268;10269	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974
N2AB	3348	10267;10268;10269	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974
N2A	3348	10267;10268;10269	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974
N2B	3302	10129;10130;10131	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974
Novex-1	3302	10129;10130;10131	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974
Novex-2	3302	10129;10130;10131	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974
Novex-3	3348	10267;10268;10269	chr2:178764249;178764248;178764247	chr2:179628976;179628975;179628974

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-24
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5164
• 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
I/S	None	None	0.062	N	0.314	0.231	0.722308813073	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	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
I/A	0.387	ambiguous	0.4683	ambiguous	-1.212	Destabilizing	0.035	N	0.306	neutral	None	None	None	None	I
I/C	0.788	likely_pathogenic	0.7326	pathogenic	-0.765	Destabilizing	0.824	D	0.325	neutral	None	None	None	None	I
I/D	0.732	likely_pathogenic	0.7912	pathogenic	-0.655	Destabilizing	0.555	D	0.377	neutral	None	None	None	None	I
I/E	0.5388	ambiguous	0.6414	pathogenic	-0.731	Destabilizing	0.555	D	0.374	neutral	None	None	None	None	I
I/F	0.1843	likely_benign	0.2111	benign	-1.032	Destabilizing	0.317	N	0.307	neutral	D	0.622766937	None	None	I
I/G	0.7204	likely_pathogenic	0.7615	pathogenic	-1.424	Destabilizing	0.262	N	0.382	neutral	None	None	None	None	I
I/H	0.5269	ambiguous	0.5641	pathogenic	-0.558	Destabilizing	0.935	D	0.312	neutral	None	None	None	None	I
I/K	0.4343	ambiguous	0.5065	ambiguous	-0.729	Destabilizing	0.555	D	0.379	neutral	None	None	None	None	I
I/L	0.103	likely_benign	0.1187	benign	-0.751	Destabilizing	None	N	0.092	neutral	N	0.472726605	None	None	I
I/M	0.1105	likely_benign	0.1265	benign	-0.546	Destabilizing	0.317	N	0.347	neutral	N	0.521530718	None	None	I
I/N	0.3334	likely_benign	0.402	ambiguous	-0.515	Destabilizing	0.484	N	0.367	neutral	D	0.548951751	None	None	I
I/P	0.9001	likely_pathogenic	0.8956	pathogenic	-0.871	Destabilizing	0.791	D	0.367	neutral	None	None	None	None	I
I/Q	0.426	ambiguous	0.5115	ambiguous	-0.799	Destabilizing	0.791	D	0.343	neutral	None	None	None	None	I
I/R	0.3472	ambiguous	0.3967	ambiguous	-0.039	Destabilizing	0.555	D	0.366	neutral	None	None	None	None	I
I/S	0.3527	ambiguous	0.4175	ambiguous	-1.031	Destabilizing	0.062	N	0.314	neutral	N	0.504515433	None	None	I
I/T	0.2452	likely_benign	0.3021	benign	-1.004	Destabilizing	0.002	N	0.141	neutral	N	0.470658997	None	None	I
I/V	0.0781	likely_benign	0.0778	benign	-0.871	Destabilizing	None	N	0.127	neutral	N	0.448989289	None	None	I
I/W	0.8232	likely_pathogenic	0.8286	pathogenic	-1.0	Destabilizing	0.935	D	0.365	neutral	None	None	None	None	I
I/Y	0.5394	ambiguous	0.5537	ambiguous	-0.79	Destabilizing	0.555	D	0.367	neutral	None	None	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.