TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35725	107398;107399;107400	chr2:178528578;178528577;178528576	chr2:179393305;179393304;179393303
N2AB	34084	102475;102476;102477	chr2:178528578;178528577;178528576	chr2:179393305;179393304;179393303
N2A	33157	99694;99695;99696	chr2:178528578;178528577;178528576	chr2:179393305;179393304;179393303
N2B	26660	80203;80204;80205	chr2:178528578;178528577;178528576	chr2:179393305;179393304;179393303
Novex-1	26785	80578;80579;80580	chr2:178528578;178528577;178528576	chr2:179393305;179393304;179393303
Novex-2	26852	80779;80780;80781	chr2:178528578;178528577;178528576	chr2:179393305;179393304;179393303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-168
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0851
• 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/V	rs1687594887	None	None	N	0.215	0.15	0.199424873507	gnomAD-4.0.0	3.18728E-06	None	None	None	None	N	None	5.66123E-05	0	None	0	0	None	0	0	2.86226E-06	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
I/A	0.9321	likely_pathogenic	0.9019	pathogenic	-2.824	Highly Destabilizing	0.035	N	0.663	neutral	None	None	None	None	N
I/C	0.9705	likely_pathogenic	0.9634	pathogenic	-2.111	Highly Destabilizing	0.824	D	0.755	deleterious	None	None	None	None	N
I/D	0.9975	likely_pathogenic	0.9958	pathogenic	-3.154	Highly Destabilizing	0.555	D	0.821	deleterious	None	None	None	None	N
I/E	0.9938	likely_pathogenic	0.99	pathogenic	-2.897	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/F	0.5961	likely_pathogenic	0.5264	ambiguous	-1.666	Destabilizing	0.317	N	0.749	deleterious	D	0.522712051	None	None	N
I/G	0.9898	likely_pathogenic	0.9848	pathogenic	-3.398	Highly Destabilizing	0.555	D	0.794	deleterious	None	None	None	None	N
I/H	0.9929	likely_pathogenic	0.9888	pathogenic	-2.813	Highly Destabilizing	0.935	D	0.8	deleterious	None	None	None	None	N
I/K	0.9861	likely_pathogenic	0.9784	pathogenic	-2.059	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
I/L	0.3194	likely_benign	0.2822	benign	-1.138	Destabilizing	None	N	0.235	neutral	N	0.519690389	None	None	N
I/M	0.3278	likely_benign	0.28	benign	-1.183	Destabilizing	0.317	N	0.682	prob.neutral	N	0.506121805	None	None	N
I/N	0.9683	likely_pathogenic	0.9515	pathogenic	-2.498	Highly Destabilizing	0.741	D	0.823	deleterious	N	0.517985089	None	None	N
I/P	0.9962	likely_pathogenic	0.9944	pathogenic	-1.685	Destabilizing	0.791	D	0.822	deleterious	None	None	None	None	N
I/Q	0.9898	likely_pathogenic	0.9842	pathogenic	-2.31	Highly Destabilizing	0.791	D	0.819	deleterious	None	None	None	None	N
I/R	0.9826	likely_pathogenic	0.9732	pathogenic	-1.828	Destabilizing	0.555	D	0.823	deleterious	None	None	None	None	N
I/S	0.9632	likely_pathogenic	0.9447	pathogenic	-3.212	Highly Destabilizing	0.317	N	0.769	deleterious	N	0.511476338	None	None	N
I/T	0.9197	likely_pathogenic	0.8805	pathogenic	-2.805	Highly Destabilizing	0.062	N	0.713	prob.delet.	N	0.462490312	None	None	N
I/V	0.1234	likely_benign	0.1206	benign	-1.685	Destabilizing	None	N	0.215	neutral	N	0.372646594	None	None	N
I/W	0.9919	likely_pathogenic	0.9877	pathogenic	-2.054	Highly Destabilizing	0.935	D	0.801	deleterious	None	None	None	None	N
I/Y	0.9449	likely_pathogenic	0.9243	pathogenic	-1.821	Destabilizing	0.555	D	0.781	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.