TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1146	3661;3662;3663	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933
N2AB	1146	3661;3662;3663	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933
N2A	1146	3661;3662;3663	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933
N2B	1100	3523;3524;3525	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933
Novex-1	1100	3523;3524;3525	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933
Novex-2	1100	3523;3524;3525	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933
Novex-3	1146	3661;3662;3663	chr2:178781208;178781207;178781206	chr2:179645935;179645934;179645933

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-4
• Domain position: 65
• Structural Position: 144
• Q(SASA): 0.1141
• 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	None	None	0.51	N	0.518	0.306	0.233785782151	gnomAD-4.0.0	1.59077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8568E-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	0.2117	likely_benign	0.1829	benign	-1.551	Destabilizing	0.51	D	0.518	neutral	N	0.424090651	None	None	N
T/C	0.7087	likely_pathogenic	0.6755	pathogenic	-1.482	Destabilizing	0.994	D	0.708	prob.delet.	None	None	None	None	N
T/D	0.9826	likely_pathogenic	0.9868	pathogenic	-1.843	Destabilizing	0.959	D	0.705	prob.neutral	None	None	None	None	N
T/E	0.9826	likely_pathogenic	0.9861	pathogenic	-1.674	Destabilizing	0.921	D	0.701	prob.neutral	None	None	None	None	N
T/F	0.9627	likely_pathogenic	0.9666	pathogenic	-1.428	Destabilizing	0.979	D	0.751	deleterious	None	None	None	None	N
T/G	0.7423	likely_pathogenic	0.759	pathogenic	-1.882	Destabilizing	0.769	D	0.642	neutral	None	None	None	None	N
T/H	0.9655	likely_pathogenic	0.9733	pathogenic	-1.856	Destabilizing	0.994	D	0.73	prob.delet.	None	None	None	None	N
T/I	0.7629	likely_pathogenic	0.7775	pathogenic	-0.693	Destabilizing	0.946	D	0.743	deleterious	N	0.408275847	None	None	N
T/K	0.974	likely_pathogenic	0.9809	pathogenic	-0.802	Destabilizing	0.921	D	0.702	prob.neutral	None	None	None	None	N
T/L	0.391	ambiguous	0.4073	ambiguous	-0.693	Destabilizing	0.87	D	0.639	neutral	None	None	None	None	N
T/M	0.4051	ambiguous	0.4163	ambiguous	-0.703	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
T/N	0.7503	likely_pathogenic	0.7973	pathogenic	-1.397	Destabilizing	0.898	D	0.74	deleterious	N	0.5112759	None	None	N
T/P	0.6017	likely_pathogenic	0.661	pathogenic	-0.953	Destabilizing	0.946	D	0.746	deleterious	N	0.491083414	None	None	N
T/Q	0.9532	likely_pathogenic	0.9637	pathogenic	-1.357	Destabilizing	0.959	D	0.742	deleterious	None	None	None	None	N
T/R	0.9562	likely_pathogenic	0.9661	pathogenic	-0.793	Destabilizing	0.959	D	0.749	deleterious	None	None	None	None	N
T/S	0.3769	ambiguous	0.4087	ambiguous	-1.651	Destabilizing	0.016	N	0.393	neutral	N	0.493644121	None	None	N
T/V	0.5156	ambiguous	0.5194	ambiguous	-0.953	Destabilizing	0.87	D	0.616	neutral	None	None	None	None	N
T/W	0.995	likely_pathogenic	0.9964	pathogenic	-1.447	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
T/Y	0.9736	likely_pathogenic	0.9792	pathogenic	-1.113	Destabilizing	0.979	D	0.748	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.