TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8174	24745;24746;24747	chr2:178718586;178718585;178718584	chr2:179583313;179583312;179583311
N2AB	7857	23794;23795;23796	chr2:178718586;178718585;178718584	chr2:179583313;179583312;179583311
N2A	6930	21013;21014;21015	chr2:178718586;178718585;178718584	chr2:179583313;179583312;179583311
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-67
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4631
• 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/M	rs727504961	None	0.454	N	0.276	0.219	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs727504961	None	0.454	N	0.276	0.219	None	gnomAD-4.0.0	3.10159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.24185E-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	0.2405	likely_benign	0.2239	benign	-0.782	Destabilizing	0.454	N	0.3	neutral	N	0.478595762	None	None	N
V/C	0.8123	likely_pathogenic	0.7346	pathogenic	-0.751	Destabilizing	0.998	D	0.371	neutral	None	None	None	None	N
V/D	0.4416	ambiguous	0.4158	ambiguous	-0.104	Destabilizing	0.949	D	0.425	neutral	None	None	None	None	N
V/E	0.2401	likely_benign	0.2148	benign	-0.171	Destabilizing	0.934	D	0.399	neutral	N	0.46963254	None	None	N
V/F	0.2155	likely_benign	0.1818	benign	-0.699	Destabilizing	0.037	N	0.241	neutral	None	None	None	None	N
V/G	0.2608	likely_benign	0.2447	benign	-0.988	Destabilizing	0.801	D	0.394	neutral	N	0.502575821	None	None	N
V/H	0.5576	ambiguous	0.4936	ambiguous	-0.383	Destabilizing	0.998	D	0.414	neutral	None	None	None	None	N
V/I	0.0786	likely_benign	0.0771	benign	-0.367	Destabilizing	0.525	D	0.304	neutral	None	None	None	None	N
V/K	0.3163	likely_benign	0.2723	benign	-0.592	Destabilizing	0.949	D	0.396	neutral	None	None	None	None	N
V/L	0.1781	likely_benign	0.1553	benign	-0.367	Destabilizing	0.223	N	0.315	neutral	N	0.504556994	None	None	N
V/M	0.1596	likely_benign	0.1418	benign	-0.391	Destabilizing	0.454	N	0.276	neutral	N	0.472608281	None	None	N
V/N	0.3236	likely_benign	0.3092	benign	-0.393	Destabilizing	0.949	D	0.436	neutral	None	None	None	None	N
V/P	0.8785	likely_pathogenic	0.8662	pathogenic	-0.469	Destabilizing	0.974	D	0.408	neutral	None	None	None	None	N
V/Q	0.2449	likely_benign	0.223	benign	-0.58	Destabilizing	0.974	D	0.407	neutral	None	None	None	None	N
V/R	0.2853	likely_benign	0.2496	benign	-0.085	Destabilizing	0.974	D	0.434	neutral	None	None	None	None	N
V/S	0.2196	likely_benign	0.2195	benign	-0.904	Destabilizing	0.172	N	0.249	neutral	None	None	None	None	N
V/T	0.1892	likely_benign	0.1814	benign	-0.859	Destabilizing	0.067	N	0.161	neutral	None	None	None	None	N
V/W	0.8399	likely_pathogenic	0.7745	pathogenic	-0.779	Destabilizing	0.998	D	0.452	neutral	None	None	None	None	N
V/Y	0.6047	likely_pathogenic	0.5363	ambiguous	-0.492	Destabilizing	0.904	D	0.389	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.