TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24685	74278;74279;74280	chr2:178572079;178572078;178572077	chr2:179436806;179436805;179436804
N2AB	23044	69355;69356;69357	chr2:178572079;178572078;178572077	chr2:179436806;179436805;179436804
N2A	22117	66574;66575;66576	chr2:178572079;178572078;178572077	chr2:179436806;179436805;179436804
N2B	15620	47083;47084;47085	chr2:178572079;178572078;178572077	chr2:179436806;179436805;179436804
Novex-1	15745	47458;47459;47460	chr2:178572079;178572078;178572077	chr2:179436806;179436805;179436804
Novex-2	15812	47659;47660;47661	chr2:178572079;178572078;178572077	chr2:179436806;179436805;179436804
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-67
• Domain position: 70
• Structural Position: 104
• Q(SASA): 0.0892
• 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
Y/S	None	None	0.992	D	0.848	0.859	0.898978955884	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
Y/A	0.9945	likely_pathogenic	0.9933	pathogenic	-3.178	Highly Destabilizing	0.989	D	0.852	deleterious	None	None	None	None	N
Y/C	0.946	likely_pathogenic	0.9386	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.649022935	None	None	N
Y/D	0.9973	likely_pathogenic	0.9962	pathogenic	-3.405	Highly Destabilizing	0.992	D	0.872	deleterious	D	0.681293822	None	None	N
Y/E	0.9991	likely_pathogenic	0.9988	pathogenic	-3.208	Highly Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	N
Y/F	0.4068	ambiguous	0.3723	ambiguous	-1.13	Destabilizing	0.981	D	0.728	prob.delet.	D	0.602166755	None	None	N
Y/G	0.9853	likely_pathogenic	0.9812	pathogenic	-3.602	Highly Destabilizing	0.979	D	0.866	deleterious	None	None	None	None	N
Y/H	0.9836	likely_pathogenic	0.9788	pathogenic	-2.09	Highly Destabilizing	0.993	D	0.797	deleterious	D	0.665042296	None	None	N
Y/I	0.9624	likely_pathogenic	0.9611	pathogenic	-1.771	Destabilizing	0.963	D	0.832	deleterious	None	None	None	None	N
Y/K	0.9984	likely_pathogenic	0.9978	pathogenic	-2.295	Highly Destabilizing	0.975	D	0.859	deleterious	None	None	None	None	N
Y/L	0.9389	likely_pathogenic	0.9291	pathogenic	-1.771	Destabilizing	0.88	D	0.806	deleterious	None	None	None	None	N
Y/M	0.9779	likely_pathogenic	0.9738	pathogenic	-1.561	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
Y/N	0.9725	likely_pathogenic	0.9631	pathogenic	-3.048	Highly Destabilizing	0.338	N	0.724	prob.delet.	D	0.681092018	None	None	N
Y/P	0.9995	likely_pathogenic	0.9994	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/Q	0.9984	likely_pathogenic	0.9977	pathogenic	-2.822	Highly Destabilizing	0.99	D	0.833	deleterious	None	None	None	None	N
Y/R	0.9958	likely_pathogenic	0.9946	pathogenic	-1.993	Destabilizing	0.993	D	0.874	deleterious	None	None	None	None	N
Y/S	0.9887	likely_pathogenic	0.9858	pathogenic	-3.449	Highly Destabilizing	0.992	D	0.848	deleterious	D	0.681293822	None	None	N
Y/T	0.9938	likely_pathogenic	0.9931	pathogenic	-3.13	Highly Destabilizing	0.997	D	0.854	deleterious	None	None	None	None	N
Y/V	0.9208	likely_pathogenic	0.9277	pathogenic	-2.255	Highly Destabilizing	0.998	D	0.818	deleterious	None	None	None	None	N
Y/W	0.9416	likely_pathogenic	0.9305	pathogenic	-0.441	Destabilizing	1.0	D	0.78	deleterious	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.