TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22635	68128;68129;68130	chr2:178579127;178579126;178579125	chr2:179443854;179443853;179443852
N2AB	20994	63205;63206;63207	chr2:178579127;178579126;178579125	chr2:179443854;179443853;179443852
N2A	20067	60424;60425;60426	chr2:178579127;178579126;178579125	chr2:179443854;179443853;179443852
N2B	13570	40933;40934;40935	chr2:178579127;178579126;178579125	chr2:179443854;179443853;179443852
Novex-1	13695	41308;41309;41310	chr2:178579127;178579126;178579125	chr2:179443854;179443853;179443852
Novex-2	13762	41509;41510;41511	chr2:178579127;178579126;178579125	chr2:179443854;179443853;179443852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-127
• Domain position: 76
• Structural Position: 171
• Q(SASA): 0.7057
• 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
T/N	None	None	0.051	N	0.208	0.22	0.303123707472	gnomAD-4.0.0	3.42178E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49805E-06	0	0
T/S	rs1465804178	None	0.051	N	0.177	0.09	0.154104182512	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1465804178	None	0.051	N	0.177	0.09	0.154104182512	gnomAD-4.0.0	6.57626E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47128E-05	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	0.0777	likely_benign	0.0757	benign	-0.303	Destabilizing	0.022	N	0.165	neutral	N	0.508931891	None	None	I
T/C	0.2841	likely_benign	0.2803	benign	-0.268	Destabilizing	0.998	D	0.506	neutral	None	None	None	None	I
T/D	0.2918	likely_benign	0.2708	benign	0.283	Stabilizing	0.728	D	0.467	neutral	None	None	None	None	I
T/E	0.24	likely_benign	0.2208	benign	0.205	Stabilizing	0.842	D	0.441	neutral	None	None	None	None	I
T/F	0.1684	likely_benign	0.1632	benign	-0.816	Destabilizing	0.991	D	0.534	neutral	None	None	None	None	I
T/G	0.2223	likely_benign	0.2098	benign	-0.422	Destabilizing	0.525	D	0.513	neutral	None	None	None	None	I
T/H	0.1889	likely_benign	0.1863	benign	-0.691	Destabilizing	0.974	D	0.532	neutral	None	None	None	None	I
T/I	0.1029	likely_benign	0.0985	benign	-0.112	Destabilizing	0.966	D	0.494	neutral	D	0.531520749	None	None	I
T/K	0.1821	likely_benign	0.1729	benign	-0.297	Destabilizing	0.029	N	0.193	neutral	None	None	None	None	I
T/L	0.0911	likely_benign	0.086	benign	-0.112	Destabilizing	0.842	D	0.442	neutral	None	None	None	None	I
T/M	0.0822	likely_benign	0.081	benign	-0.015	Destabilizing	0.991	D	0.509	neutral	None	None	None	None	I
T/N	0.0903	likely_benign	0.0883	benign	-0.083	Destabilizing	0.051	N	0.208	neutral	N	0.517263372	None	None	I
T/P	0.1781	likely_benign	0.1662	benign	-0.147	Destabilizing	0.891	D	0.492	neutral	D	0.531867465	None	None	I
T/Q	0.1725	likely_benign	0.1668	benign	-0.298	Destabilizing	0.949	D	0.491	neutral	None	None	None	None	I
T/R	0.1558	likely_benign	0.1505	benign	-0.042	Destabilizing	0.728	D	0.45	neutral	None	None	None	None	I
T/S	0.0913	likely_benign	0.0897	benign	-0.301	Destabilizing	0.051	N	0.177	neutral	N	0.488959263	None	None	I
T/V	0.0904	likely_benign	0.0895	benign	-0.147	Destabilizing	0.842	D	0.304	neutral	None	None	None	None	I
T/W	0.5115	ambiguous	0.4792	ambiguous	-0.835	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	I
T/Y	0.2201	likely_benign	0.2085	benign	-0.54	Destabilizing	0.991	D	0.533	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.