TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19074	57445;57446;57447	chr2:178597950;178597949;178597948	chr2:179462677;179462676;179462675
N2AB	17433	52522;52523;52524	chr2:178597950;178597949;178597948	chr2:179462677;179462676;179462675
N2A	16506	49741;49742;49743	chr2:178597950;178597949;178597948	chr2:179462677;179462676;179462675
N2B	10009	30250;30251;30252	chr2:178597950;178597949;178597948	chr2:179462677;179462676;179462675
Novex-1	10134	30625;30626;30627	chr2:178597950;178597949;178597948	chr2:179462677;179462676;179462675
Novex-2	10201	30826;30827;30828	chr2:178597950;178597949;178597948	chr2:179462677;179462676;179462675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-26
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2858
• 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
P/R	None	None	0.999	N	0.853	0.434	0.604919980721	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8599E-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
P/A	0.0932	likely_benign	0.0987	benign	-1.56	Destabilizing	0.767	D	0.451	neutral	N	0.477734659	None	None	N
P/C	0.6829	likely_pathogenic	0.6857	pathogenic	-0.901	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/D	0.808	likely_pathogenic	0.8194	pathogenic	-1.533	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/E	0.6518	likely_pathogenic	0.6663	pathogenic	-1.576	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/F	0.716	likely_pathogenic	0.751	pathogenic	-1.308	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/G	0.6134	likely_pathogenic	0.6169	pathogenic	-1.823	Destabilizing	0.997	D	0.731	prob.delet.	None	None	None	None	N
P/H	0.537	ambiguous	0.5262	ambiguous	-1.275	Destabilizing	1.0	D	0.847	deleterious	N	0.521251005	None	None	N
P/I	0.5946	likely_pathogenic	0.6114	pathogenic	-0.946	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/K	0.7948	likely_pathogenic	0.7979	pathogenic	-1.257	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/L	0.3806	ambiguous	0.3891	ambiguous	-0.946	Destabilizing	0.999	D	0.78	deleterious	N	0.510411224	None	None	N
P/M	0.6087	likely_pathogenic	0.6197	pathogenic	-0.661	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/N	0.7758	likely_pathogenic	0.7748	pathogenic	-0.959	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/Q	0.58	likely_pathogenic	0.5706	pathogenic	-1.233	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/R	0.6865	likely_pathogenic	0.6799	pathogenic	-0.607	Destabilizing	0.999	D	0.853	deleterious	N	0.502132791	None	None	N
P/S	0.307	likely_benign	0.2981	benign	-1.399	Destabilizing	0.998	D	0.721	prob.delet.	N	0.496599383	None	None	N
P/T	0.2724	likely_benign	0.2636	benign	-1.354	Destabilizing	0.999	D	0.722	prob.delet.	N	0.504196706	None	None	N
P/V	0.4199	ambiguous	0.4348	ambiguous	-1.118	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
P/W	0.836	likely_pathogenic	0.8443	pathogenic	-1.415	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/Y	0.7349	likely_pathogenic	0.7467	pathogenic	-1.182	Destabilizing	1.0	D	0.873	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.