TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5294	16105;16106;16107	chr2:178733413;178733412;178733411	chr2:179598140;179598139;179598138
N2AB	4977	15154;15155;15156	chr2:178733413;178733412;178733411	chr2:179598140;179598139;179598138
N2A	4050	12373;12374;12375	chr2:178733413;178733412;178733411	chr2:179598140;179598139;179598138
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-36
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.098
• 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
W/L	None	None	1.0	D	0.837	0.868	0.964309650005	gnomAD-4.0.0	6.36511E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14333E-05	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
W/A	0.9394	likely_pathogenic	0.9584	pathogenic	-2.306	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
W/C	0.9445	likely_pathogenic	0.9739	pathogenic	-1.243	Destabilizing	1.0	D	0.831	deleterious	D	0.748686039	None	None	N
W/D	0.9988	likely_pathogenic	0.9987	pathogenic	-3.113	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
W/E	0.9982	likely_pathogenic	0.998	pathogenic	-2.979	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
W/F	0.4103	ambiguous	0.4434	ambiguous	-1.494	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
W/G	0.8846	likely_pathogenic	0.9123	pathogenic	-2.559	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.774967143	None	None	N
W/H	0.9916	likely_pathogenic	0.9912	pathogenic	-2.219	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
W/I	0.8106	likely_pathogenic	0.8594	pathogenic	-1.364	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
W/K	0.9993	likely_pathogenic	0.9993	pathogenic	-2.287	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
W/L	0.7642	likely_pathogenic	0.8233	pathogenic	-1.364	Destabilizing	1.0	D	0.837	deleterious	D	0.774967143	None	None	N
W/M	0.9087	likely_pathogenic	0.9412	pathogenic	-0.975	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
W/N	0.9965	likely_pathogenic	0.9963	pathogenic	-3.085	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
W/P	0.9963	likely_pathogenic	0.9964	pathogenic	-1.705	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
W/Q	0.9983	likely_pathogenic	0.9986	pathogenic	-2.755	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
W/R	0.9982	likely_pathogenic	0.9983	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.774902048	None	None	N
W/S	0.9604	likely_pathogenic	0.9702	pathogenic	-3.088	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.774902048	None	None	N
W/T	0.968	likely_pathogenic	0.974	pathogenic	-2.869	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
W/V	0.8179	likely_pathogenic	0.8688	pathogenic	-1.705	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
W/Y	0.7954	likely_pathogenic	0.8167	pathogenic	-1.389	Destabilizing	1.0	D	0.821	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.