TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1090	3493;3494;3495	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049
N2AB	1090	3493;3494;3495	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049
N2A	1090	3493;3494;3495	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049
N2B	1044	3355;3356;3357	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049
Novex-1	1044	3355;3356;3357	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049
Novex-2	1044	3355;3356;3357	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049
Novex-3	1090	3493;3494;3495	chr2:178782324;178782323;178782322	chr2:179647051;179647050;179647049

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-4
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3991
• 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
V/I	rs1419239601	None	None	N	0.127	0.104	0.259761712551	gnomAD-4.0.0	1.36815E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99298E-07	0	1.6559E-05

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
V/A	0.219	likely_benign	0.2138	benign	-0.692	Destabilizing	None	N	0.063	neutral	N	0.426370641	None	None	I
V/C	0.8916	likely_pathogenic	0.8715	pathogenic	-0.683	Destabilizing	0.824	D	0.364	neutral	None	None	None	None	I
V/D	0.6553	likely_pathogenic	0.624	pathogenic	-0.272	Destabilizing	0.317	N	0.387	neutral	N	0.36842078	None	None	I
V/E	0.4884	ambiguous	0.4673	ambiguous	-0.334	Destabilizing	0.149	N	0.331	neutral	None	None	None	None	I
V/F	0.3069	likely_benign	0.2752	benign	-0.624	Destabilizing	0.317	N	0.381	neutral	N	0.448477429	None	None	I
V/G	0.392	ambiguous	0.3704	ambiguous	-0.899	Destabilizing	0.062	N	0.332	neutral	N	0.432824249	None	None	I
V/H	0.8202	likely_pathogenic	0.7905	pathogenic	-0.336	Destabilizing	0.935	D	0.373	neutral	None	None	None	None	I
V/I	0.1005	likely_benign	0.0929	benign	-0.273	Destabilizing	None	N	0.127	neutral	N	0.440976982	None	None	I
V/K	0.6418	likely_pathogenic	0.6115	pathogenic	-0.586	Destabilizing	0.149	N	0.327	neutral	None	None	None	None	I
V/L	0.33	likely_benign	0.2902	benign	-0.273	Destabilizing	0.004	N	0.252	neutral	N	0.437487752	None	None	I
V/M	0.2378	likely_benign	0.2133	benign	-0.394	Destabilizing	0.016	N	0.227	neutral	None	None	None	None	I
V/N	0.5134	ambiguous	0.4949	ambiguous	-0.395	Destabilizing	0.555	D	0.39	neutral	None	None	None	None	I
V/P	0.387	ambiguous	0.3858	ambiguous	-0.376	Destabilizing	0.001	N	0.262	neutral	None	None	None	None	I
V/Q	0.5186	ambiguous	0.5023	ambiguous	-0.573	Destabilizing	0.555	D	0.367	neutral	None	None	None	None	I
V/R	0.5672	likely_pathogenic	0.541	ambiguous	-0.092	Destabilizing	0.38	N	0.389	neutral	None	None	None	None	I
V/S	0.3002	likely_benign	0.2909	benign	-0.839	Destabilizing	0.081	N	0.285	neutral	None	None	None	None	I
V/T	0.2834	likely_benign	0.273	benign	-0.79	Destabilizing	0.081	N	0.161	neutral	None	None	None	None	I
V/W	0.9247	likely_pathogenic	0.9068	pathogenic	-0.736	Destabilizing	0.935	D	0.447	neutral	None	None	None	None	I
V/Y	0.778	likely_pathogenic	0.7556	pathogenic	-0.435	Destabilizing	0.555	D	0.377	neutral	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.