TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8764	26515;26516;26517	chr2:178714484;178714483;178714482	chr2:179579211;179579210;179579209
N2AB	8447	25564;25565;25566	chr2:178714484;178714483;178714482	chr2:179579211;179579210;179579209
N2A	7520	22783;22784;22785	chr2:178714484;178714483;178714482	chr2:179579211;179579210;179579209
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-73
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6546
• Predicted PPI site: I

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/S	None	None	1.0	N	0.694	0.483	0.512825096792	gnomAD-4.0.0	2.7373E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59826E-06	0	0
P/T	None	None	1.0	N	0.686	0.469	0.54173910141	gnomAD-4.0.0	6.84326E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65706E-05

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	0.1899	likely_benign	0.2195	benign	-0.418	Destabilizing	0.999	D	0.655	neutral	N	0.49736503	None	None	I
P/C	0.8191	likely_pathogenic	0.858	pathogenic	-0.576	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
P/D	0.5446	ambiguous	0.6067	pathogenic	-0.447	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
P/E	0.4673	ambiguous	0.5439	ambiguous	-0.577	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/F	0.7342	likely_pathogenic	0.7956	pathogenic	-0.762	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
P/G	0.5115	ambiguous	0.5652	pathogenic	-0.521	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/H	0.3981	ambiguous	0.4653	ambiguous	-0.147	Destabilizing	1.0	D	0.642	neutral	D	0.527612512	None	None	I
P/I	0.579	likely_pathogenic	0.6441	pathogenic	-0.302	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
P/K	0.5033	ambiguous	0.5581	ambiguous	-0.428	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
P/L	0.2752	likely_benign	0.3258	benign	-0.302	Destabilizing	1.0	D	0.701	prob.neutral	N	0.510722798	None	None	I
P/M	0.5207	ambiguous	0.5868	pathogenic	-0.351	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
P/N	0.4439	ambiguous	0.5014	ambiguous	-0.129	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/Q	0.3501	ambiguous	0.4086	ambiguous	-0.406	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
P/R	0.3854	ambiguous	0.4448	ambiguous	0.111	Stabilizing	1.0	D	0.684	prob.neutral	N	0.500353998	None	None	I
P/S	0.2855	likely_benign	0.3423	ambiguous	-0.43	Destabilizing	1.0	D	0.694	prob.neutral	N	0.499593529	None	None	I
P/T	0.2244	likely_benign	0.2785	benign	-0.467	Destabilizing	1.0	D	0.686	prob.neutral	N	0.495617057	None	None	I
P/V	0.4355	ambiguous	0.4917	ambiguous	-0.307	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
P/W	0.861	likely_pathogenic	0.9004	pathogenic	-0.834	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
P/Y	0.6723	likely_pathogenic	0.732	pathogenic	-0.534	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I

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.