TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25471	76636;76637;76638	chr2:178569721;178569720;178569719	chr2:179434448;179434447;179434446
N2AB	23830	71713;71714;71715	chr2:178569721;178569720;178569719	chr2:179434448;179434447;179434446
N2A	22903	68932;68933;68934	chr2:178569721;178569720;178569719	chr2:179434448;179434447;179434446
N2B	16406	49441;49442;49443	chr2:178569721;178569720;178569719	chr2:179434448;179434447;179434446
Novex-1	16531	49816;49817;49818	chr2:178569721;178569720;178569719	chr2:179434448;179434447;179434446
Novex-2	16598	50017;50018;50019	chr2:178569721;178569720;178569719	chr2:179434448;179434447;179434446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-73
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.1061
• 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
L/M	None	None	1.0	D	0.845	0.54	0.819663918045	gnomAD-4.0.0	2.0534E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99591E-07	2.31932E-05	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
L/A	0.9106	likely_pathogenic	0.9108	pathogenic	-2.479	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
L/C	0.8701	likely_pathogenic	0.8945	pathogenic	-1.833	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9964	likely_pathogenic	0.9961	pathogenic	-2.42	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/E	0.986	likely_pathogenic	0.9857	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/F	0.6879	likely_pathogenic	0.6566	pathogenic	-1.537	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/G	0.9756	likely_pathogenic	0.9727	pathogenic	-3.041	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/H	0.9718	likely_pathogenic	0.969	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/I	0.2551	likely_benign	0.2489	benign	-0.858	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
L/K	0.9832	likely_pathogenic	0.98	pathogenic	-1.806	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/M	0.3785	ambiguous	0.3667	ambiguous	-0.844	Destabilizing	1.0	D	0.845	deleterious	D	0.606702914	None	None	N
L/N	0.9778	likely_pathogenic	0.9789	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/P	0.9731	likely_pathogenic	0.9708	pathogenic	-1.378	Destabilizing	1.0	D	0.853	deleterious	D	0.663229648	None	None	N
L/Q	0.9541	likely_pathogenic	0.9525	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.646978122	None	None	N
L/R	0.9668	likely_pathogenic	0.9622	pathogenic	-1.561	Destabilizing	1.0	D	0.853	deleterious	D	0.663229648	None	None	N
L/S	0.9795	likely_pathogenic	0.9803	pathogenic	-2.943	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/T	0.9175	likely_pathogenic	0.9222	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/V	0.3003	likely_benign	0.2896	benign	-1.378	Destabilizing	0.999	D	0.836	deleterious	D	0.592571231	None	None	N
L/W	0.9555	likely_pathogenic	0.9457	pathogenic	-1.858	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
L/Y	0.9411	likely_pathogenic	0.9337	pathogenic	-1.559	Destabilizing	1.0	D	0.835	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.