TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16808	50647;50648;50649	chr2:178611887;178611886;178611885	chr2:179476614;179476613;179476612
N2AB	15167	45724;45725;45726	chr2:178611887;178611886;178611885	chr2:179476614;179476613;179476612
N2A	14240	42943;42944;42945	chr2:178611887;178611886;178611885	chr2:179476614;179476613;179476612
N2B	7743	23452;23453;23454	chr2:178611887;178611886;178611885	chr2:179476614;179476613;179476612
Novex-1	7868	23827;23828;23829	chr2:178611887;178611886;178611885	chr2:179476614;179476613;179476612
Novex-2	7935	24028;24029;24030	chr2:178611887;178611886;178611885	chr2:179476614;179476613;179476612
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-10
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.6908
• 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
D/N	None	None	0.999	N	0.66	0.291	0.394837016283	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.2806	likely_benign	0.2034	benign	-0.363	Destabilizing	0.999	D	0.649	neutral	N	0.481373009	None	None	I
D/C	0.8314	likely_pathogenic	0.7406	pathogenic	-0.034	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
D/E	0.2059	likely_benign	0.1711	benign	-0.444	Destabilizing	0.767	D	0.274	neutral	N	0.466182362	None	None	I
D/F	0.7906	likely_pathogenic	0.6912	pathogenic	-0.257	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
D/G	0.3555	ambiguous	0.2505	benign	-0.599	Destabilizing	0.998	D	0.71	prob.delet.	N	0.482432455	None	None	I
D/H	0.535	ambiguous	0.4142	ambiguous	-0.263	Destabilizing	1.0	D	0.725	prob.delet.	N	0.468217259	None	None	I
D/I	0.5274	ambiguous	0.4165	ambiguous	0.221	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
D/K	0.6369	likely_pathogenic	0.5136	ambiguous	0.054	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
D/L	0.5664	likely_pathogenic	0.4642	ambiguous	0.221	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/M	0.8056	likely_pathogenic	0.718	pathogenic	0.43	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/N	0.1504	likely_benign	0.1163	benign	-0.223	Destabilizing	0.999	D	0.66	neutral	N	0.478369469	None	None	I
D/P	0.8782	likely_pathogenic	0.8252	pathogenic	0.05	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
D/Q	0.5219	ambiguous	0.4187	ambiguous	-0.17	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
D/R	0.6946	likely_pathogenic	0.5812	pathogenic	0.232	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
D/S	0.2062	likely_benign	0.1522	benign	-0.359	Destabilizing	0.997	D	0.653	neutral	None	None	None	None	I
D/T	0.3852	ambiguous	0.2951	benign	-0.178	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
D/V	0.3267	likely_benign	0.2459	benign	0.05	Stabilizing	0.999	D	0.747	deleterious	N	0.481367287	None	None	I
D/W	0.9715	likely_pathogenic	0.9525	pathogenic	-0.123	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
D/Y	0.4564	ambiguous	0.3556	ambiguous	-0.028	Destabilizing	1.0	D	0.731	prob.delet.	N	0.492565797	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.