TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15612	47059;47060;47061	chr2:178618716;178618715;178618714	chr2:179483443;179483442;179483441
N2AB	13971	42136;42137;42138	chr2:178618716;178618715;178618714	chr2:179483443;179483442;179483441
N2A	13044	39355;39356;39357	chr2:178618716;178618715;178618714	chr2:179483443;179483442;179483441
N2B	6547	19864;19865;19866	chr2:178618716;178618715;178618714	chr2:179483443;179483442;179483441
Novex-1	6672	20239;20240;20241	chr2:178618716;178618715;178618714	chr2:179483443;179483442;179483441
Novex-2	6739	20440;20441;20442	chr2:178618716;178618715;178618714	chr2:179483443;179483442;179483441
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-108
• Domain position: 45
• Structural Position: 122
• Q(SASA): 0.5202
• 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	rs2057779557	None	0.454	N	0.262	0.11	0.186928172975	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs2057779557	None	0.454	N	0.262	0.11	0.186928172975	gnomAD-4.0.0	6.58519E-06	None	None	None	None	N	None	2.41604E-05	0	None	0	0	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	0.069	likely_benign	0.0768	benign	-0.775	Destabilizing	0.454	N	0.262	neutral	N	0.500444872	None	None	N
T/C	0.299	likely_benign	0.3405	ambiguous	-0.381	Destabilizing	0.998	D	0.405	neutral	None	None	None	None	N
T/D	0.1558	likely_benign	0.2131	benign	0.846	Stabilizing	0.728	D	0.332	neutral	None	None	None	None	N
T/E	0.1484	likely_benign	0.1953	benign	0.853	Stabilizing	0.842	D	0.333	neutral	None	None	None	None	N
T/F	0.1409	likely_benign	0.1786	benign	-0.987	Destabilizing	0.974	D	0.417	neutral	None	None	None	None	N
T/G	0.1364	likely_benign	0.1625	benign	-1.002	Destabilizing	0.007	N	0.231	neutral	None	None	None	None	N
T/H	0.1461	likely_benign	0.1765	benign	-1.163	Destabilizing	0.037	N	0.236	neutral	None	None	None	None	N
T/I	0.1325	likely_benign	0.1609	benign	-0.268	Destabilizing	0.966	D	0.455	neutral	N	0.489807163	None	None	N
T/K	0.1475	likely_benign	0.1915	benign	-0.151	Destabilizing	0.842	D	0.347	neutral	None	None	None	None	N
T/L	0.0838	likely_benign	0.0947	benign	-0.268	Destabilizing	0.842	D	0.359	neutral	None	None	None	None	N
T/M	0.0785	likely_benign	0.0864	benign	-0.181	Destabilizing	0.998	D	0.399	neutral	None	None	None	None	N
T/N	0.0622	likely_benign	0.0705	benign	-0.111	Destabilizing	0.022	N	0.1	neutral	N	0.462995559	None	None	N
T/P	0.1094	likely_benign	0.1208	benign	-0.406	Destabilizing	0.966	D	0.451	neutral	N	0.503577223	None	None	N
T/Q	0.1455	likely_benign	0.1708	benign	-0.184	Destabilizing	0.949	D	0.459	neutral	None	None	None	None	N
T/R	0.1353	likely_benign	0.1761	benign	-0.074	Destabilizing	0.842	D	0.443	neutral	None	None	None	None	N
T/S	0.0765	likely_benign	0.0912	benign	-0.542	Destabilizing	0.136	N	0.123	neutral	N	0.477023038	None	None	N
T/V	0.1131	likely_benign	0.1333	benign	-0.406	Destabilizing	0.915	D	0.273	neutral	None	None	None	None	N
T/W	0.3783	ambiguous	0.4387	ambiguous	-0.904	Destabilizing	0.998	D	0.441	neutral	None	None	None	None	N
T/Y	0.1339	likely_benign	0.1569	benign	-0.632	Destabilizing	0.949	D	0.422	neutral	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.