TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7408	22447;22448;22449	chr2:178722677;178722676;178722675	chr2:179587404;179587403;179587402
N2AB	7091	21496;21497;21498	chr2:178722677;178722676;178722675	chr2:179587404;179587403;179587402
N2A	6164	18715;18716;18717	chr2:178722677;178722676;178722675	chr2:179587404;179587403;179587402
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-58
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0977
• 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
T/I	None	None	0.642	N	0.681	0.235	0.419713421852	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	6.07533E-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
T/A	0.0618	likely_benign	0.0626	benign	-1.193	Destabilizing	0.001	N	0.123	neutral	N	0.387464118	None	None	N
T/C	0.3955	ambiguous	0.4201	ambiguous	-0.828	Destabilizing	0.003	N	0.349	neutral	None	None	None	None	N
T/D	0.6257	likely_pathogenic	0.7887	pathogenic	-0.685	Destabilizing	0.704	D	0.684	prob.neutral	None	None	None	None	N
T/E	0.5484	ambiguous	0.7383	pathogenic	-0.566	Destabilizing	0.704	D	0.673	neutral	None	None	None	None	N
T/F	0.4493	ambiguous	0.6674	pathogenic	-0.976	Destabilizing	0.944	D	0.743	deleterious	None	None	None	None	N
T/G	0.2244	likely_benign	0.2817	benign	-1.551	Destabilizing	0.329	N	0.621	neutral	None	None	None	None	N
T/H	0.4879	ambiguous	0.6786	pathogenic	-1.674	Destabilizing	0.981	D	0.713	prob.delet.	None	None	None	None	N
T/I	0.2809	likely_benign	0.4638	ambiguous	-0.284	Destabilizing	0.642	D	0.681	prob.neutral	N	0.488457831	None	None	N
T/K	0.4586	ambiguous	0.6693	pathogenic	-0.596	Destabilizing	0.704	D	0.667	neutral	None	None	None	None	N
T/L	0.1855	likely_benign	0.2743	benign	-0.284	Destabilizing	0.495	N	0.601	neutral	None	None	None	None	N
T/M	0.1044	likely_benign	0.141	benign	-0.175	Destabilizing	0.981	D	0.72	prob.delet.	None	None	None	None	N
T/N	0.2288	likely_benign	0.3492	ambiguous	-0.91	Destabilizing	0.642	D	0.611	neutral	N	0.489264409	None	None	N
T/P	0.6072	likely_pathogenic	0.8123	pathogenic	-0.555	Destabilizing	0.784	D	0.75	deleterious	N	0.507758455	None	None	N
T/Q	0.4373	ambiguous	0.6131	pathogenic	-0.892	Destabilizing	0.944	D	0.752	deleterious	None	None	None	None	N
T/R	0.3735	ambiguous	0.5645	pathogenic	-0.615	Destabilizing	0.704	D	0.754	deleterious	None	None	None	None	N
T/S	0.1289	likely_benign	0.159	benign	-1.261	Destabilizing	0.01	N	0.139	neutral	N	0.477262189	None	None	N
T/V	0.1753	likely_benign	0.2382	benign	-0.555	Destabilizing	0.329	N	0.505	neutral	None	None	None	None	N
T/W	0.8173	likely_pathogenic	0.9255	pathogenic	-0.929	Destabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
T/Y	0.4823	ambiguous	0.6843	pathogenic	-0.64	Destabilizing	0.981	D	0.738	prob.delet.	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.