TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7813	23662;23663;23664	chr2:178720205;178720204;178720203	chr2:179584932;179584931;179584930
N2AB	7496	22711;22712;22713	chr2:178720205;178720204;178720203	chr2:179584932;179584931;179584930
N2A	6569	19930;19931;19932	chr2:178720205;178720204;178720203	chr2:179584932;179584931;179584930
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-63
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5175
• 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
E/Q	None	None	0.001	N	0.323	0.146	0.0551355673512	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.1668	likely_benign	0.1295	benign	-0.719	Destabilizing	None	N	0.308	neutral	N	0.467425545	None	None	N
E/C	0.8743	likely_pathogenic	0.8455	pathogenic	-0.29	Destabilizing	0.883	D	0.463	neutral	None	None	None	None	N
E/D	0.2222	likely_benign	0.1854	benign	-0.715	Destabilizing	0.001	N	0.229	neutral	N	0.484645869	None	None	N
E/F	0.7392	likely_pathogenic	0.6561	pathogenic	-0.344	Destabilizing	0.667	D	0.474	neutral	None	None	None	None	N
E/G	0.2292	likely_benign	0.1923	benign	-0.995	Destabilizing	None	N	0.344	neutral	N	0.468872072	None	None	N
E/H	0.4686	ambiguous	0.4075	ambiguous	-0.321	Destabilizing	0.497	N	0.469	neutral	None	None	None	None	N
E/I	0.3674	ambiguous	0.2845	benign	0.006	Stabilizing	0.124	N	0.5	neutral	None	None	None	None	N
E/K	0.2087	likely_benign	0.1653	benign	-0.075	Destabilizing	0.042	N	0.481	neutral	N	0.430464667	None	None	N
E/L	0.4315	ambiguous	0.3414	ambiguous	0.006	Stabilizing	0.124	N	0.491	neutral	None	None	None	None	N
E/M	0.4808	ambiguous	0.3943	ambiguous	0.247	Stabilizing	0.667	D	0.466	neutral	None	None	None	None	N
E/N	0.3383	likely_benign	0.2737	benign	-0.543	Destabilizing	0.22	N	0.431	neutral	None	None	None	None	N
E/P	0.846	likely_pathogenic	0.7855	pathogenic	-0.215	Destabilizing	0.364	N	0.5	neutral	None	None	None	None	N
E/Q	0.1283	likely_benign	0.115	benign	-0.475	Destabilizing	0.001	N	0.323	neutral	N	0.427021717	None	None	N
E/R	0.3179	likely_benign	0.2727	benign	0.202	Stabilizing	0.124	N	0.433	neutral	None	None	None	None	N
E/S	0.2057	likely_benign	0.1694	benign	-0.74	Destabilizing	0.011	N	0.253	neutral	None	None	None	None	N
E/T	0.1962	likely_benign	0.1544	benign	-0.512	Destabilizing	0.055	N	0.506	neutral	None	None	None	None	N
E/V	0.2086	likely_benign	0.1622	benign	-0.215	Destabilizing	0.003	N	0.387	neutral	N	0.474946163	None	None	N
E/W	0.9001	likely_pathogenic	0.8625	pathogenic	-0.086	Destabilizing	0.958	D	0.49	neutral	None	None	None	None	N
E/Y	0.6471	likely_pathogenic	0.5635	ambiguous	-0.081	Destabilizing	0.667	D	0.468	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.