TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22735	68428;68429;68430	chr2:178578827;178578826;178578825	chr2:179443554;179443553;179443552
N2AB	21094	63505;63506;63507	chr2:178578827;178578826;178578825	chr2:179443554;179443553;179443552
N2A	20167	60724;60725;60726	chr2:178578827;178578826;178578825	chr2:179443554;179443553;179443552
N2B	13670	41233;41234;41235	chr2:178578827;178578826;178578825	chr2:179443554;179443553;179443552
Novex-1	13795	41608;41609;41610	chr2:178578827;178578826;178578825	chr2:179443554;179443553;179443552
Novex-2	13862	41809;41810;41811	chr2:178578827;178578826;178578825	chr2:179443554;179443553;179443552
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-52
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.154
• 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
I/F	rs2154174995	None	0.314	N	0.508	0.182	0.480349945188	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78927E-04
I/F	rs2154174995	None	0.314	N	0.508	0.182	0.480349945188	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.73934E-04

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	0.2498	likely_benign	0.1389	benign	-2.096	Highly Destabilizing	0.034	N	0.521	neutral	None	None	None	None	N
I/C	0.5384	ambiguous	0.4611	ambiguous	-1.335	Destabilizing	0.823	D	0.593	neutral	None	None	None	None	N
I/D	0.9044	likely_pathogenic	0.7393	pathogenic	-1.929	Destabilizing	0.552	D	0.795	deleterious	None	None	None	None	N
I/E	0.7111	likely_pathogenic	0.4801	ambiguous	-1.74	Destabilizing	0.552	D	0.779	deleterious	None	None	None	None	N
I/F	0.2175	likely_benign	0.1406	benign	-1.221	Destabilizing	0.314	N	0.508	neutral	N	0.466124864	None	None	N
I/G	0.7571	likely_pathogenic	0.5375	ambiguous	-2.576	Highly Destabilizing	0.552	D	0.751	deleterious	None	None	None	None	N
I/H	0.6309	likely_pathogenic	0.4545	ambiguous	-1.681	Destabilizing	0.934	D	0.816	deleterious	None	None	None	None	N
I/K	0.448	ambiguous	0.3027	benign	-1.499	Destabilizing	0.552	D	0.777	deleterious	None	None	None	None	N
I/L	0.1133	likely_benign	0.0956	benign	-0.742	Destabilizing	0.012	N	0.327	neutral	N	0.513358197	None	None	N
I/M	0.0892	likely_benign	0.0733	benign	-0.676	Destabilizing	0.314	N	0.53	neutral	N	0.495391298	None	None	N
I/N	0.6061	likely_pathogenic	0.3833	ambiguous	-1.779	Destabilizing	0.739	D	0.809	deleterious	N	0.503093843	None	None	N
I/P	0.9634	likely_pathogenic	0.9037	pathogenic	-1.172	Destabilizing	0.552	D	0.798	deleterious	None	None	None	None	N
I/Q	0.5053	ambiguous	0.3429	ambiguous	-1.694	Destabilizing	0.789	D	0.811	deleterious	None	None	None	None	N
I/R	0.3727	ambiguous	0.2369	benign	-1.167	Destabilizing	0.552	D	0.808	deleterious	None	None	None	None	N
I/S	0.4102	ambiguous	0.2349	benign	-2.48	Highly Destabilizing	0.314	N	0.708	prob.delet.	N	0.488531079	None	None	N
I/T	0.1591	likely_benign	0.0881	benign	-2.139	Highly Destabilizing	0.061	N	0.591	neutral	N	0.474314391	None	None	N
I/V	0.05	likely_benign	0.0478	benign	-1.172	Destabilizing	None	N	0.149	neutral	N	0.408537531	None	None	N
I/W	0.8584	likely_pathogenic	0.7469	pathogenic	-1.438	Destabilizing	0.934	D	0.808	deleterious	None	None	None	None	N
I/Y	0.6422	likely_pathogenic	0.5103	ambiguous	-1.145	Destabilizing	0.552	D	0.593	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.