TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33265	100018;100019;100020	chr2:178537414;178537413;178537412	chr2:179402141;179402140;179402139
N2AB	31624	95095;95096;95097	chr2:178537414;178537413;178537412	chr2:179402141;179402140;179402139
N2A	30697	92314;92315;92316	chr2:178537414;178537413;178537412	chr2:179402141;179402140;179402139
N2B	24200	72823;72824;72825	chr2:178537414;178537413;178537412	chr2:179402141;179402140;179402139
Novex-1	24325	73198;73199;73200	chr2:178537414;178537413;178537412	chr2:179402141;179402140;179402139
Novex-2	24392	73399;73400;73401	chr2:178537414;178537413;178537412	chr2:179402141;179402140;179402139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-157
• Domain position: 63
• Structural Position: 151
• Q(SASA): 0.1921
• 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
A/T	None	None	0.631	N	0.335	0.12	0.212008924253	gnomAD-4.0.0	6.8572E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01297E-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
A/C	0.5833	likely_pathogenic	0.6135	pathogenic	-0.827	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
A/D	0.5674	likely_pathogenic	0.5608	ambiguous	-1.064	Destabilizing	0.997	D	0.785	deleterious	N	0.486657516	None	None	N
A/E	0.3985	ambiguous	0.3742	ambiguous	-1.045	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
A/F	0.5026	ambiguous	0.5238	ambiguous	-0.911	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/G	0.1589	likely_benign	0.1649	benign	-1.206	Destabilizing	0.804	D	0.43	neutral	N	0.483036156	None	None	N
A/H	0.6376	likely_pathogenic	0.6403	pathogenic	-1.413	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
A/I	0.4108	ambiguous	0.4223	ambiguous	-0.171	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
A/K	0.5162	ambiguous	0.5069	ambiguous	-1.037	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
A/L	0.3333	likely_benign	0.3225	benign	-0.171	Destabilizing	0.998	D	0.562	neutral	None	None	None	None	N
A/M	0.3573	ambiguous	0.3694	ambiguous	-0.157	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
A/N	0.4662	ambiguous	0.4711	ambiguous	-0.848	Destabilizing	0.979	D	0.806	deleterious	None	None	None	None	N
A/P	0.8431	likely_pathogenic	0.8482	pathogenic	-0.368	Destabilizing	0.998	D	0.797	deleterious	N	0.499281269	None	None	N
A/Q	0.4141	ambiguous	0.3936	ambiguous	-0.924	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/R	0.398	ambiguous	0.383	ambiguous	-0.816	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
A/S	0.1086	likely_benign	0.1093	benign	-1.278	Destabilizing	0.077	N	0.355	neutral	N	0.45736692	None	None	N
A/T	0.1199	likely_benign	0.1225	benign	-1.151	Destabilizing	0.631	D	0.335	neutral	N	0.483689516	None	None	N
A/V	0.2169	likely_benign	0.219	benign	-0.368	Destabilizing	0.992	D	0.479	neutral	N	0.486911005	None	None	N
A/W	0.8809	likely_pathogenic	0.8807	pathogenic	-1.344	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
A/Y	0.6854	likely_pathogenic	0.7015	pathogenic	-0.881	Destabilizing	1.0	D	0.847	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.