TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14043	42352;42353;42354	chr2:178634747;178634746;178634745	chr2:179499474;179499473;179499472
N2AB	12402	37429;37430;37431	chr2:178634747;178634746;178634745	chr2:179499474;179499473;179499472
N2A	11475	34648;34649;34650	chr2:178634747;178634746;178634745	chr2:179499474;179499473;179499472
N2B	4978	15157;15158;15159	chr2:178634747;178634746;178634745	chr2:179499474;179499473;179499472
Novex-1	5103	15532;15533;15534	chr2:178634747;178634746;178634745	chr2:179499474;179499473;179499472
Novex-2	5170	15733;15734;15735	chr2:178634747;178634746;178634745	chr2:179499474;179499473;179499472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-90
• Domain position: 79
• Structural Position: 164
• Q(SASA): 0.1302
• 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/P	None	None	0.999	N	0.863	0.475	0.371903410333	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.6525	likely_pathogenic	0.3837	ambiguous	-0.642	Destabilizing	0.997	D	0.567	neutral	N	0.418881652	None	None	N
T/C	0.8859	likely_pathogenic	0.7856	pathogenic	-0.349	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
T/D	0.9857	likely_pathogenic	0.9536	pathogenic	-0.261	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
T/E	0.9895	likely_pathogenic	0.956	pathogenic	-0.123	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
T/F	0.9862	likely_pathogenic	0.9652	pathogenic	-0.462	Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
T/G	0.8307	likely_pathogenic	0.6509	pathogenic	-1.011	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
T/H	0.9608	likely_pathogenic	0.9	pathogenic	-1.122	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
T/I	0.9845	likely_pathogenic	0.9458	pathogenic	0.29	Stabilizing	0.999	D	0.864	deleterious	N	0.490229209	None	None	N
T/K	0.9872	likely_pathogenic	0.9522	pathogenic	-0.195	Destabilizing	0.999	D	0.842	deleterious	N	0.488418668	None	None	N
T/L	0.9351	likely_pathogenic	0.842	pathogenic	0.29	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
T/M	0.8754	likely_pathogenic	0.6767	pathogenic	0.145	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/N	0.9102	likely_pathogenic	0.756	pathogenic	-0.634	Destabilizing	0.999	D	0.697	prob.delet.	None	None	None	None	N
T/P	0.983	likely_pathogenic	0.964	pathogenic	0.013	Stabilizing	0.999	D	0.863	deleterious	N	0.489259926	None	None	N
T/Q	0.9635	likely_pathogenic	0.8906	pathogenic	-0.48	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
T/R	0.9798	likely_pathogenic	0.9399	pathogenic	-0.313	Destabilizing	0.999	D	0.862	deleterious	N	0.450782112	None	None	N
T/S	0.5092	ambiguous	0.2825	benign	-0.921	Destabilizing	0.997	D	0.545	neutral	N	0.431996154	None	None	N
T/V	0.9082	likely_pathogenic	0.8015	pathogenic	0.013	Stabilizing	0.998	D	0.574	neutral	None	None	None	None	N
T/W	0.9962	likely_pathogenic	0.9899	pathogenic	-0.577	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/Y	0.9836	likely_pathogenic	0.9605	pathogenic	-0.188	Destabilizing	1.0	D	0.903	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.