TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5283	16072;16073;16074	chr2:178733446;178733445;178733444	chr2:179598173;179598172;179598171
N2AB	4966	15121;15122;15123	chr2:178733446;178733445;178733444	chr2:179598173;179598172;179598171
N2A	4039	12340;12341;12342	chr2:178733446;178733445;178733444	chr2:179598173;179598172;179598171
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-36
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1451
• 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/R	None	None	0.188	N	0.601	0.204	0.669087604336	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
T/A	0.0768	likely_benign	0.0948	benign	-0.984	Destabilizing	0.002	N	0.264	neutral	N	0.514201528	None	None	N
T/C	0.3816	ambiguous	0.4521	ambiguous	-0.806	Destabilizing	0.935	D	0.563	neutral	None	None	None	None	N
T/D	0.4671	ambiguous	0.5869	pathogenic	-1.167	Destabilizing	0.555	D	0.603	neutral	None	None	None	None	N
T/E	0.2733	likely_benign	0.3559	ambiguous	-1.045	Destabilizing	0.149	N	0.579	neutral	None	None	None	None	N
T/F	0.2257	likely_benign	0.3064	benign	-0.659	Destabilizing	0.38	N	0.598	neutral	None	None	None	None	N
T/G	0.2924	likely_benign	0.3966	ambiguous	-1.354	Destabilizing	0.149	N	0.596	neutral	None	None	None	None	N
T/H	0.2183	likely_benign	0.2691	benign	-1.579	Destabilizing	0.935	D	0.583	neutral	None	None	None	None	N
T/I	0.1119	likely_benign	0.1468	benign	-0.046	Destabilizing	0.004	N	0.389	neutral	N	0.51848684	None	None	N
T/K	0.129	likely_benign	0.1549	benign	-0.865	Destabilizing	0.002	N	0.395	neutral	N	0.464576953	None	None	N
T/L	0.0831	likely_benign	0.1102	benign	-0.046	Destabilizing	0.012	N	0.527	neutral	None	None	None	None	N
T/M	0.0761	likely_benign	0.0913	benign	-0.018	Destabilizing	0.012	N	0.507	neutral	None	None	None	None	N
T/N	0.1523	likely_benign	0.1839	benign	-1.232	Destabilizing	0.555	D	0.577	neutral	None	None	None	None	N
T/P	0.257	likely_benign	0.366	ambiguous	-0.326	Destabilizing	0.484	N	0.603	neutral	N	0.516521741	None	None	N
T/Q	0.1785	likely_benign	0.2187	benign	-1.161	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	N
T/R	0.1023	likely_benign	0.1264	benign	-0.877	Destabilizing	0.188	N	0.601	neutral	N	0.509862529	None	None	N
T/S	0.1251	likely_benign	0.1491	benign	-1.43	Destabilizing	0.062	N	0.506	neutral	N	0.514065105	None	None	N
T/V	0.0925	likely_benign	0.1143	benign	-0.326	Destabilizing	0.035	N	0.507	neutral	None	None	None	None	N
T/W	0.5603	ambiguous	0.6862	pathogenic	-0.747	Destabilizing	0.935	D	0.613	neutral	None	None	None	None	N
T/Y	0.2838	likely_benign	0.3493	ambiguous	-0.433	Destabilizing	0.555	D	0.61	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.