TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17576	52951;52952;52953	chr2:178608061;178608060;178608059	chr2:179472788;179472787;179472786
N2AB	15935	48028;48029;48030	chr2:178608061;178608060;178608059	chr2:179472788;179472787;179472786
N2A	15008	45247;45248;45249	chr2:178608061;178608060;178608059	chr2:179472788;179472787;179472786
N2B	8511	25756;25757;25758	chr2:178608061;178608060;178608059	chr2:179472788;179472787;179472786
Novex-1	8636	26131;26132;26133	chr2:178608061;178608060;178608059	chr2:179472788;179472787;179472786
Novex-2	8703	26332;26333;26334	chr2:178608061;178608060;178608059	chr2:179472788;179472787;179472786
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-16
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2995
• 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/L	None	None	0.999	N	0.83	0.373	0.468336420597	gnomAD-4.0.0	1.36953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79978E-06	0	0
P/S	None	None	0.992	N	0.77	0.354	0.340273420219	gnomAD-4.0.0	4.79342E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.2993E-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	0.3748	ambiguous	0.3675	ambiguous	-1.933	Destabilizing	0.767	D	0.417	neutral	N	0.511323543	None	None	N
P/C	0.8411	likely_pathogenic	0.8289	pathogenic	-1.364	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/D	0.9954	likely_pathogenic	0.9956	pathogenic	-2.642	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/E	0.9856	likely_pathogenic	0.9857	pathogenic	-2.492	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/F	0.9762	likely_pathogenic	0.9709	pathogenic	-1.172	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/G	0.9217	likely_pathogenic	0.9237	pathogenic	-2.397	Highly Destabilizing	0.997	D	0.763	deleterious	None	None	None	None	N
P/H	0.9733	likely_pathogenic	0.9687	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/I	0.7525	likely_pathogenic	0.7308	pathogenic	-0.668	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/K	0.9893	likely_pathogenic	0.9884	pathogenic	-1.758	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/L	0.5727	likely_pathogenic	0.5435	ambiguous	-0.668	Destabilizing	0.999	D	0.83	deleterious	N	0.433659688	None	None	N
P/M	0.9032	likely_pathogenic	0.8945	pathogenic	-0.6	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/N	0.9846	likely_pathogenic	0.9837	pathogenic	-1.872	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/Q	0.9641	likely_pathogenic	0.9621	pathogenic	-1.823	Destabilizing	1.0	D	0.845	deleterious	N	0.500944704	None	None	N
P/R	0.9658	likely_pathogenic	0.9606	pathogenic	-1.453	Destabilizing	0.999	D	0.874	deleterious	N	0.512301009	None	None	N
P/S	0.8617	likely_pathogenic	0.8532	pathogenic	-2.384	Highly Destabilizing	0.992	D	0.77	deleterious	N	0.51204752	None	None	N
P/T	0.767	likely_pathogenic	0.754	pathogenic	-2.12	Highly Destabilizing	0.999	D	0.816	deleterious	N	0.500437725	None	None	N
P/V	0.5467	ambiguous	0.5293	ambiguous	-1.062	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
P/W	0.9939	likely_pathogenic	0.9923	pathogenic	-1.713	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/Y	0.9862	likely_pathogenic	0.9824	pathogenic	-1.344	Destabilizing	1.0	D	0.89	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.