TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1317	4174;4175;4176	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968
N2AB	1317	4174;4175;4176	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968
N2A	1317	4174;4175;4176	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968
N2B	1271	4036;4037;4038	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968
Novex-1	1271	4036;4037;4038	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968
Novex-2	1271	4036;4037;4038	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968
Novex-3	1317	4174;4175;4176	chr2:178779243;178779242;178779241	chr2:179643970;179643969;179643968

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-5
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.7433
• 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
Y/C	rs775768014	None	0.998	N	0.469	0.434	0.676397002788	gnomAD-4.0.0	1.36852E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.319E-05	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
Y/A	0.7128	likely_pathogenic	0.7355	pathogenic	-0.278	Destabilizing	0.584	D	0.485	neutral	None	None	None	None	I
Y/C	0.3838	ambiguous	0.3843	ambiguous	0.082	Stabilizing	0.998	D	0.469	neutral	N	0.509792889	None	None	I
Y/D	0.5838	likely_pathogenic	0.5777	pathogenic	0.671	Stabilizing	0.719	D	0.522	neutral	N	0.463333782	None	None	I
Y/E	0.7865	likely_pathogenic	0.8014	pathogenic	0.638	Stabilizing	0.737	D	0.517	neutral	None	None	None	None	I
Y/F	0.112	likely_benign	0.1153	benign	-0.263	Destabilizing	0.912	D	0.457	neutral	N	0.491848464	None	None	I
Y/G	0.7812	likely_pathogenic	0.7953	pathogenic	-0.403	Destabilizing	0.737	D	0.539	neutral	None	None	None	None	I
Y/H	0.2856	likely_benign	0.2935	benign	0.337	Stabilizing	0.016	N	0.288	neutral	N	0.494514319	None	None	I
Y/I	0.5841	likely_pathogenic	0.6019	pathogenic	0.007	Stabilizing	0.932	D	0.487	neutral	None	None	None	None	I
Y/K	0.7236	likely_pathogenic	0.7375	pathogenic	0.25	Stabilizing	0.037	N	0.289	neutral	None	None	None	None	I
Y/L	0.5926	likely_pathogenic	0.6187	pathogenic	0.007	Stabilizing	0.85	D	0.445	neutral	None	None	None	None	I
Y/M	0.6792	likely_pathogenic	0.7029	pathogenic	-0.115	Destabilizing	0.993	D	0.459	neutral	None	None	None	None	I
Y/N	0.2367	likely_benign	0.2392	benign	-0.003	Destabilizing	0.064	N	0.334	neutral	N	0.402888413	None	None	I
Y/P	0.9611	likely_pathogenic	0.9702	pathogenic	-0.07	Destabilizing	0.932	D	0.517	neutral	None	None	None	None	I
Y/Q	0.6541	likely_pathogenic	0.6841	pathogenic	0.08	Stabilizing	0.872	D	0.493	neutral	None	None	None	None	I
Y/R	0.6089	likely_pathogenic	0.622	pathogenic	0.346	Stabilizing	0.021	N	0.361	neutral	None	None	None	None	I
Y/S	0.3036	likely_benign	0.3166	benign	-0.283	Destabilizing	0.166	N	0.332	neutral	N	0.455831742	None	None	I
Y/T	0.5357	ambiguous	0.568	pathogenic	-0.233	Destabilizing	0.584	D	0.487	neutral	None	None	None	None	I
Y/V	0.5061	ambiguous	0.5318	ambiguous	-0.07	Destabilizing	0.932	D	0.512	neutral	None	None	None	None	I
Y/W	0.6103	likely_pathogenic	0.622	pathogenic	-0.539	Destabilizing	0.998	D	0.447	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.