TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13971	42136;42137;42138	chr2:178635278;178635277;178635276	chr2:179500005;179500004;179500003
N2AB	12330	37213;37214;37215	chr2:178635278;178635277;178635276	chr2:179500005;179500004;179500003
N2A	11403	34432;34433;34434	chr2:178635278;178635277;178635276	chr2:179500005;179500004;179500003
N2B	4906	14941;14942;14943	chr2:178635278;178635277;178635276	chr2:179500005;179500004;179500003
Novex-1	5031	15316;15317;15318	chr2:178635278;178635277;178635276	chr2:179500005;179500004;179500003
Novex-2	5098	15517;15518;15519	chr2:178635278;178635277;178635276	chr2:179500005;179500004;179500003
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-90
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.123
• 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/M	None	None	0.664	N	0.678	0.056	0.193865811164	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86004E-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	0.8199	likely_pathogenic	0.7491	pathogenic	-2.546	Highly Destabilizing	0.236	N	0.575	neutral	None	None	None	None	N
I/C	0.9788	likely_pathogenic	0.9579	pathogenic	-1.887	Destabilizing	0.942	D	0.639	neutral	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9973	pathogenic	-2.813	Highly Destabilizing	0.942	D	0.811	deleterious	None	None	None	None	N
I/E	0.9946	likely_pathogenic	0.9912	pathogenic	-2.6	Highly Destabilizing	0.842	D	0.818	deleterious	None	None	None	None	N
I/F	0.9278	likely_pathogenic	0.8498	pathogenic	-1.453	Destabilizing	0.272	N	0.661	prob.neutral	None	None	None	None	N
I/G	0.9919	likely_pathogenic	0.9812	pathogenic	-3.087	Highly Destabilizing	0.842	D	0.789	deleterious	None	None	None	None	N
I/H	0.9986	likely_pathogenic	0.9961	pathogenic	-2.513	Highly Destabilizing	0.984	D	0.743	deleterious	None	None	None	None	N
I/K	0.9938	likely_pathogenic	0.9869	pathogenic	-1.954	Destabilizing	0.534	D	0.771	deleterious	N	0.435079279	None	None	N
I/L	0.2273	likely_benign	0.1235	benign	-0.991	Destabilizing	None	N	0.143	neutral	N	0.331927265	None	None	N
I/M	0.3974	ambiguous	0.2412	benign	-1.021	Destabilizing	0.664	D	0.678	prob.neutral	N	0.433216058	None	None	N
I/N	0.9898	likely_pathogenic	0.9766	pathogenic	-2.231	Highly Destabilizing	0.942	D	0.809	deleterious	None	None	None	None	N
I/P	0.9382	likely_pathogenic	0.9021	pathogenic	-1.489	Destabilizing	0.942	D	0.813	deleterious	None	None	None	None	N
I/Q	0.9938	likely_pathogenic	0.9864	pathogenic	-2.118	Highly Destabilizing	0.942	D	0.803	deleterious	None	None	None	None	N
I/R	0.9918	likely_pathogenic	0.9822	pathogenic	-1.652	Destabilizing	0.8	D	0.808	deleterious	N	0.435079279	None	None	N
I/S	0.9674	likely_pathogenic	0.9411	pathogenic	-2.933	Highly Destabilizing	0.603	D	0.653	prob.neutral	None	None	None	None	N
I/T	0.8488	likely_pathogenic	0.7713	pathogenic	-2.577	Highly Destabilizing	0.361	N	0.633	neutral	N	0.434315403	None	None	N
I/V	0.1471	likely_benign	0.1238	benign	-1.489	Destabilizing	0.022	N	0.399	neutral	N	0.432991937	None	None	N
I/W	0.9981	likely_pathogenic	0.996	pathogenic	-1.827	Destabilizing	0.984	D	0.758	deleterious	None	None	None	None	N
I/Y	0.9964	likely_pathogenic	0.9915	pathogenic	-1.554	Destabilizing	0.842	D	0.758	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.