TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16743	50452;50453;50454	chr2:178612298;178612297;178612296	chr2:179477025;179477024;179477023
N2AB	15102	45529;45530;45531	chr2:178612298;178612297;178612296	chr2:179477025;179477024;179477023
N2A	14175	42748;42749;42750	chr2:178612298;178612297;178612296	chr2:179477025;179477024;179477023
N2B	7678	23257;23258;23259	chr2:178612298;178612297;178612296	chr2:179477025;179477024;179477023
Novex-1	7803	23632;23633;23634	chr2:178612298;178612297;178612296	chr2:179477025;179477024;179477023
Novex-2	7870	23833;23834;23835	chr2:178612298;178612297;178612296	chr2:179477025;179477024;179477023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-9
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.267
• 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
V/L	None	None	0.994	D	0.649	0.315	0.483301346737	gnomAD-4.0.0	1.59407E-06	None	None	None	None	N	None	0	0	None	0	2.79127E-05	None	0	0	0	0	0
V/M	None	None	0.999	D	0.749	0.353	0.528662862717	gnomAD-4.0.0	1.59407E-06	None	None	None	None	N	None	0	0	None	0	2.79127E-05	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
V/A	0.8219	likely_pathogenic	0.7783	pathogenic	-1.373	Destabilizing	0.997	D	0.672	prob.neutral	D	0.717403803	None	None	N
V/C	0.9268	likely_pathogenic	0.9257	pathogenic	-0.893	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/D	0.9864	likely_pathogenic	0.9807	pathogenic	-1.296	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
V/E	0.938	likely_pathogenic	0.928	pathogenic	-1.105	Destabilizing	0.999	D	0.89	deleterious	D	0.681370389	None	None	N
V/F	0.6217	likely_pathogenic	0.5762	pathogenic	-0.743	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
V/G	0.939	likely_pathogenic	0.9182	pathogenic	-1.84	Destabilizing	0.999	D	0.853	deleterious	D	0.71840213	None	None	N
V/H	0.9704	likely_pathogenic	0.9651	pathogenic	-1.299	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/I	0.0997	likely_benign	0.0999	benign	-0.106	Destabilizing	0.995	D	0.644	neutral	None	None	None	None	N
V/K	0.9207	likely_pathogenic	0.9136	pathogenic	-1.035	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
V/L	0.5909	likely_pathogenic	0.5663	pathogenic	-0.106	Destabilizing	0.994	D	0.649	prob.neutral	D	0.548662481	None	None	N
V/M	0.5352	ambiguous	0.4904	ambiguous	-0.188	Destabilizing	0.999	D	0.749	deleterious	D	0.629346309	None	None	N
V/N	0.9526	likely_pathogenic	0.9401	pathogenic	-1.365	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/P	0.9911	likely_pathogenic	0.9876	pathogenic	-0.499	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
V/Q	0.8886	likely_pathogenic	0.8767	pathogenic	-1.195	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
V/R	0.9035	likely_pathogenic	0.8945	pathogenic	-0.934	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
V/S	0.9105	likely_pathogenic	0.8826	pathogenic	-1.993	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
V/T	0.7381	likely_pathogenic	0.7063	pathogenic	-1.648	Destabilizing	0.998	D	0.654	prob.neutral	None	None	None	None	N
V/W	0.9911	likely_pathogenic	0.9899	pathogenic	-1.109	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/Y	0.9459	likely_pathogenic	0.9347	pathogenic	-0.685	Destabilizing	0.999	D	0.863	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.