TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14782	44569;44570;44571	chr2:178629381;178629380;178629379	chr2:179494108;179494107;179494106
N2AB	13141	39646;39647;39648	chr2:178629381;178629380;178629379	chr2:179494108;179494107;179494106
N2A	12214	36865;36866;36867	chr2:178629381;178629380;178629379	chr2:179494108;179494107;179494106
N2B	5717	17374;17375;17376	chr2:178629381;178629380;178629379	chr2:179494108;179494107;179494106
Novex-1	5842	17749;17750;17751	chr2:178629381;178629380;178629379	chr2:179494108;179494107;179494106
Novex-2	5909	17950;17951;17952	chr2:178629381;178629380;178629379	chr2:179494108;179494107;179494106
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-99
• Domain position: 18
• Structural Position: 29
• Q(SASA): 0.4657
• 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/A	rs780249806	-0.785	0.962	D	0.523	0.343	0.162503812791	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
T/A	rs780249806	-0.785	0.962	D	0.523	0.343	0.162503812791	gnomAD-4.0.0	1.5931E-06	None	None	None	None	N	None	0	0	None	0	2.78552E-05	None	0	0	0	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	0.1014	likely_benign	0.1034	benign	-0.94	Destabilizing	0.962	D	0.523	neutral	D	0.570219515	None	None	N
T/C	0.555	ambiguous	0.5247	ambiguous	-0.479	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
T/D	0.554	ambiguous	0.5891	pathogenic	0.109	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
T/E	0.4434	ambiguous	0.4823	ambiguous	0.121	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
T/F	0.345	ambiguous	0.3546	ambiguous	-1.089	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
T/G	0.3596	ambiguous	0.3493	ambiguous	-1.197	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	N
T/H	0.3369	likely_benign	0.3457	ambiguous	-1.398	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/I	0.1922	likely_benign	0.1991	benign	-0.345	Destabilizing	0.999	D	0.75	deleterious	N	0.474998775	None	None	N
T/K	0.2867	likely_benign	0.3424	ambiguous	-0.579	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
T/L	0.1559	likely_benign	0.1597	benign	-0.345	Destabilizing	0.994	D	0.615	neutral	None	None	None	None	N
T/M	0.1328	likely_benign	0.1349	benign	-0.105	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/N	0.1834	likely_benign	0.195	benign	-0.551	Destabilizing	0.998	D	0.645	neutral	N	0.511692741	None	None	N
T/P	0.5312	ambiguous	0.5555	ambiguous	-0.512	Destabilizing	0.999	D	0.75	deleterious	D	0.6342865	None	None	N
T/Q	0.3011	likely_benign	0.3126	benign	-0.646	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
T/R	0.2271	likely_benign	0.2524	benign	-0.4	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
T/S	0.1331	likely_benign	0.1327	benign	-0.891	Destabilizing	0.619	D	0.353	neutral	N	0.452713789	None	None	N
T/V	0.1421	likely_benign	0.1407	benign	-0.512	Destabilizing	0.994	D	0.551	neutral	None	None	None	None	N
T/W	0.7609	likely_pathogenic	0.7505	pathogenic	-1.018	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/Y	0.4148	ambiguous	0.411	ambiguous	-0.775	Destabilizing	1.0	D	0.743	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.