TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4826	14701;14702;14703	chr2:178735970;178735969;178735968	chr2:179600697;179600696;179600695
N2AB	4509	13750;13751;13752	chr2:178735970;178735969;178735968	chr2:179600697;179600696;179600695
N2A	3582	10969;10970;10971	chr2:178735970;178735969;178735968	chr2:179600697;179600696;179600695
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-31
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.3117
• 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
T/A	rs1156737017	-0.933	0.027	D	0.561	0.228	0.249502417897	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/A	rs1156737017	-0.933	0.027	D	0.561	0.228	0.249502417897	gnomAD-4.0.0	1.59125E-06	None	None	None	None	I	None	0	0	None	0	2.77408E-05	None	0	0	0	0	0
T/N	None	None	0.741	D	0.649	0.376	0.508696012846	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85814E-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	0.1057	likely_benign	0.0895	benign	-0.873	Destabilizing	0.027	N	0.561	neutral	D	0.619291764	None	None	I
T/C	0.4512	ambiguous	0.3859	ambiguous	-0.364	Destabilizing	0.935	D	0.737	prob.delet.	None	None	None	None	I
T/D	0.7999	likely_pathogenic	0.6801	pathogenic	-0.584	Destabilizing	0.555	D	0.745	deleterious	None	None	None	None	I
T/E	0.6899	likely_pathogenic	0.5664	pathogenic	-0.527	Destabilizing	0.262	N	0.738	prob.delet.	None	None	None	None	I
T/F	0.4967	ambiguous	0.4227	ambiguous	-0.699	Destabilizing	0.38	N	0.788	deleterious	None	None	None	None	I
T/G	0.4537	ambiguous	0.3717	ambiguous	-1.194	Destabilizing	0.262	N	0.769	deleterious	None	None	None	None	I
T/H	0.5635	ambiguous	0.4388	ambiguous	-1.456	Destabilizing	0.935	D	0.819	deleterious	None	None	None	None	I
T/I	0.2117	likely_benign	0.1779	benign	-0.08	Destabilizing	None	N	0.445	neutral	N	0.380880121	None	None	I
T/K	0.4456	ambiguous	0.3317	benign	-0.897	Destabilizing	0.555	D	0.739	prob.delet.	None	None	None	None	I
T/L	0.1565	likely_benign	0.1426	benign	-0.08	Destabilizing	0.005	N	0.593	neutral	None	None	None	None	I
T/M	0.1041	likely_benign	0.1005	benign	0.138	Stabilizing	0.38	N	0.741	deleterious	None	None	None	None	I
T/N	0.2783	likely_benign	0.2107	benign	-0.895	Destabilizing	0.741	D	0.649	neutral	D	0.712066047	None	None	I
T/P	0.2896	likely_benign	0.2254	benign	-0.312	Destabilizing	0.741	D	0.743	deleterious	D	0.712066047	None	None	I
T/Q	0.5316	ambiguous	0.4244	ambiguous	-0.888	Destabilizing	0.791	D	0.751	deleterious	None	None	None	None	I
T/R	0.399	ambiguous	0.2906	benign	-0.812	Destabilizing	0.555	D	0.753	deleterious	None	None	None	None	I
T/S	0.2424	likely_benign	0.1856	benign	-1.103	Destabilizing	0.211	N	0.62	neutral	D	0.748369	None	None	I
T/V	0.1545	likely_benign	0.1331	benign	-0.312	Destabilizing	None	N	0.293	neutral	None	None	None	None	I
T/W	0.8348	likely_pathogenic	0.7574	pathogenic	-0.749	Destabilizing	0.935	D	0.815	deleterious	None	None	None	None	I
T/Y	0.4875	ambiguous	0.4114	ambiguous	-0.521	Destabilizing	0.555	D	0.816	deleterious	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.