TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15313	46162;46163;46164	chr2:178620584;178620583;178620582	chr2:179485311;179485310;179485309
N2AB	13672	41239;41240;41241	chr2:178620584;178620583;178620582	chr2:179485311;179485310;179485309
N2A	12745	38458;38459;38460	chr2:178620584;178620583;178620582	chr2:179485311;179485310;179485309
N2B	6248	18967;18968;18969	chr2:178620584;178620583;178620582	chr2:179485311;179485310;179485309
Novex-1	6373	19342;19343;19344	chr2:178620584;178620583;178620582	chr2:179485311;179485310;179485309
Novex-2	6440	19543;19544;19545	chr2:178620584;178620583;178620582	chr2:179485311;179485310;179485309
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-105
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1485
• 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	rs2058109086	None	0.999	N	0.722	0.424	0.48300943003	gnomAD-4.0.0	6.85359E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00487E-07	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	0.1631	likely_benign	0.1252	benign	-0.97	Destabilizing	0.981	D	0.487	neutral	N	0.490924545	None	None	N
T/C	0.6391	likely_pathogenic	0.5932	pathogenic	-0.688	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
T/D	0.8063	likely_pathogenic	0.7357	pathogenic	-0.932	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
T/E	0.7253	likely_pathogenic	0.6227	pathogenic	-0.806	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
T/F	0.6964	likely_pathogenic	0.5677	pathogenic	-0.504	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/G	0.5078	ambiguous	0.4723	ambiguous	-1.362	Destabilizing	0.997	D	0.645	neutral	None	None	None	None	N
T/H	0.7794	likely_pathogenic	0.6568	pathogenic	-1.529	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
T/I	0.3931	ambiguous	0.3023	benign	0.033	Stabilizing	0.999	D	0.722	prob.delet.	N	0.481849509	None	None	N
T/K	0.6972	likely_pathogenic	0.5535	ambiguous	-0.944	Destabilizing	0.999	D	0.725	prob.delet.	N	0.512650691	None	None	N
T/L	0.3388	likely_benign	0.2501	benign	0.033	Stabilizing	0.998	D	0.656	neutral	None	None	None	None	N
T/M	0.1915	likely_benign	0.1394	benign	0.111	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/N	0.3899	ambiguous	0.3157	benign	-1.244	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
T/P	0.8664	likely_pathogenic	0.8271	pathogenic	-0.268	Destabilizing	0.999	D	0.713	prob.delet.	D	0.575650028	None	None	N
T/Q	0.6359	likely_pathogenic	0.5216	ambiguous	-1.131	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
T/R	0.649	likely_pathogenic	0.4777	ambiguous	-0.98	Destabilizing	0.999	D	0.706	prob.neutral	D	0.533919147	None	None	N
T/S	0.305	likely_benign	0.261	benign	-1.492	Destabilizing	0.905	D	0.343	neutral	N	0.511407629	None	None	N
T/V	0.2711	likely_benign	0.2252	benign	-0.268	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	N
T/W	0.9334	likely_pathogenic	0.8757	pathogenic	-0.582	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
T/Y	0.7309	likely_pathogenic	0.6009	pathogenic	-0.309	Destabilizing	1.0	D	0.72	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.