TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8752	26479;26480;26481	chr2:178714520;178714519;178714518	chr2:179579247;179579246;179579245
N2AB	8435	25528;25529;25530	chr2:178714520;178714519;178714518	chr2:179579247;179579246;179579245
N2A	7508	22747;22748;22749	chr2:178714520;178714519;178714518	chr2:179579247;179579246;179579245
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-73
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4633
• 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
E/A	None	None	0.001	N	0.293	0.11	0.0986583533028	gnomAD-4.0.0	1.59258E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85984E-06	0	0
E/K	None	None	0.003	N	0.317	0.132	0.134241683229	gnomAD-4.0.0	6.84474E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99643E-07	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
E/A	0.0819	likely_benign	0.0834	benign	-0.743	Destabilizing	0.001	N	0.293	neutral	N	0.396949527	None	None	I
E/C	0.6947	likely_pathogenic	0.7115	pathogenic	-0.353	Destabilizing	0.492	N	0.257	neutral	None	None	None	None	I
E/D	0.0835	likely_benign	0.0859	benign	-0.722	Destabilizing	None	N	0.287	neutral	N	0.439025436	None	None	I
E/F	0.5271	ambiguous	0.5509	ambiguous	-0.342	Destabilizing	0.135	N	0.279	neutral	None	None	None	None	I
E/G	0.0942	likely_benign	0.1015	benign	-1.03	Destabilizing	None	N	0.169	neutral	N	0.496959018	None	None	I
E/H	0.2822	likely_benign	0.2901	benign	-0.374	Destabilizing	0.052	N	0.299	neutral	None	None	None	None	I
E/I	0.2153	likely_benign	0.2306	benign	0.014	Stabilizing	0.035	N	0.343	neutral	None	None	None	None	I
E/K	0.0932	likely_benign	0.0987	benign	-0.197	Destabilizing	0.003	N	0.317	neutral	N	0.458824705	None	None	I
E/L	0.2293	likely_benign	0.2434	benign	0.014	Stabilizing	0.005	N	0.376	neutral	None	None	None	None	I
E/M	0.2747	likely_benign	0.2912	benign	0.26	Stabilizing	0.013	N	0.259	neutral	None	None	None	None	I
E/N	0.1297	likely_benign	0.1357	benign	-0.624	Destabilizing	0.005	N	0.229	neutral	None	None	None	None	I
E/P	0.1905	likely_benign	0.1784	benign	-0.217	Destabilizing	None	N	0.188	neutral	None	None	None	None	I
E/Q	0.1049	likely_benign	0.1091	benign	-0.553	Destabilizing	None	N	0.188	neutral	N	0.427099075	None	None	I
E/R	0.1563	likely_benign	0.165	benign	0.091	Stabilizing	None	N	0.179	neutral	None	None	None	None	I
E/S	0.1145	likely_benign	0.1178	benign	-0.854	Destabilizing	None	N	0.151	neutral	None	None	None	None	I
E/T	0.1119	likely_benign	0.1175	benign	-0.619	Destabilizing	None	N	0.155	neutral	None	None	None	None	I
E/V	0.1335	likely_benign	0.1403	benign	-0.217	Destabilizing	0.003	N	0.356	neutral	N	0.459518138	None	None	I
E/W	0.6931	likely_pathogenic	0.7143	pathogenic	-0.087	Destabilizing	0.828	D	0.293	neutral	None	None	None	None	I
E/Y	0.3765	ambiguous	0.3934	ambiguous	-0.087	Destabilizing	0.295	N	0.272	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.