TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32547	97864;97865;97866	chr2:178541438;178541437;178541436	chr2:179406165;179406164;179406163
N2AB	30906	92941;92942;92943	chr2:178541438;178541437;178541436	chr2:179406165;179406164;179406163
N2A	29979	90160;90161;90162	chr2:178541438;178541437;178541436	chr2:179406165;179406164;179406163
N2B	23482	70669;70670;70671	chr2:178541438;178541437;178541436	chr2:179406165;179406164;179406163
Novex-1	23607	71044;71045;71046	chr2:178541438;178541437;178541436	chr2:179406165;179406164;179406163
Novex-2	23674	71245;71246;71247	chr2:178541438;178541437;178541436	chr2:179406165;179406164;179406163
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-125
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4337
• 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	rs1694457387	None	0.012	N	0.195	0.099	0.327952845175	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
V/A	0.2657	likely_benign	0.289	benign	-1.195	Destabilizing	0.625	D	0.352	neutral	N	0.505416291	None	None	I
V/C	0.6891	likely_pathogenic	0.6759	pathogenic	-0.792	Destabilizing	0.998	D	0.399	neutral	None	None	None	None	I
V/D	0.5854	likely_pathogenic	0.6164	pathogenic	-0.915	Destabilizing	0.989	D	0.437	neutral	N	0.507725877	None	None	I
V/E	0.3853	ambiguous	0.4049	ambiguous	-0.92	Destabilizing	0.991	D	0.413	neutral	None	None	None	None	I
V/F	0.2015	likely_benign	0.218	benign	-0.849	Destabilizing	0.934	D	0.399	neutral	N	0.506456441	None	None	I
V/G	0.286	likely_benign	0.3055	benign	-1.483	Destabilizing	0.966	D	0.41	neutral	N	0.471079296	None	None	I
V/H	0.6038	likely_pathogenic	0.6096	pathogenic	-0.937	Destabilizing	0.998	D	0.437	neutral	None	None	None	None	I
V/I	0.0732	likely_benign	0.0738	benign	-0.517	Destabilizing	0.012	N	0.195	neutral	N	0.424955352	None	None	I
V/K	0.4913	ambiguous	0.5062	ambiguous	-1.059	Destabilizing	0.974	D	0.403	neutral	None	None	None	None	I
V/L	0.1671	likely_benign	0.181	benign	-0.517	Destabilizing	0.005	N	0.135	neutral	N	0.465993898	None	None	I
V/M	0.1353	likely_benign	0.1409	benign	-0.459	Destabilizing	0.325	N	0.251	neutral	None	None	None	None	I
V/N	0.3069	likely_benign	0.3092	benign	-0.892	Destabilizing	0.991	D	0.429	neutral	None	None	None	None	I
V/P	0.9345	likely_pathogenic	0.9456	pathogenic	-0.708	Destabilizing	0.991	D	0.421	neutral	None	None	None	None	I
V/Q	0.3264	likely_benign	0.3377	benign	-1.047	Destabilizing	0.974	D	0.416	neutral	None	None	None	None	I
V/R	0.4636	ambiguous	0.4745	ambiguous	-0.528	Destabilizing	0.974	D	0.431	neutral	None	None	None	None	I
V/S	0.2684	likely_benign	0.2785	benign	-1.38	Destabilizing	0.974	D	0.372	neutral	None	None	None	None	I
V/T	0.2304	likely_benign	0.2404	benign	-1.281	Destabilizing	0.842	D	0.299	neutral	None	None	None	None	I
V/W	0.8198	likely_pathogenic	0.8381	pathogenic	-1.033	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	I
V/Y	0.5507	ambiguous	0.568	pathogenic	-0.738	Destabilizing	0.991	D	0.408	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.