TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6392	19399;19400;19401	chr2:178728752;178728751;178728750	chr2:179593479;179593478;179593477
N2AB	6075	18448;18449;18450	chr2:178728752;178728751;178728750	chr2:179593479;179593478;179593477
N2A	5148	15667;15668;15669	chr2:178728752;178728751;178728750	chr2:179593479;179593478;179593477
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-48
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.8968
• 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
K/I	rs2079823191	None	0.996	N	0.475	0.589	0.748316094813	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs2079823191	None	0.996	N	0.475	0.589	0.748316094813	gnomAD-4.0.0	6.57168E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
K/Q	rs1458174674	None	0.92	N	0.454	0.261	0.281780670237	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs1458174674	None	0.92	N	0.454	0.261	0.281780670237	gnomAD-4.0.0	6.57168E-06	None	None	None	None	N	None	2.41231E-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
K/A	0.2561	likely_benign	0.2265	benign	-0.022	Destabilizing	0.863	D	0.454	neutral	None	None	None	None	N
K/C	0.7283	likely_pathogenic	0.6901	pathogenic	-0.455	Destabilizing	0.999	D	0.464	neutral	None	None	None	None	N
K/D	0.4354	ambiguous	0.3834	ambiguous	-0.33	Destabilizing	0.046	N	0.202	neutral	None	None	None	None	N
K/E	0.1242	likely_benign	0.1129	benign	-0.352	Destabilizing	0.021	N	0.106	neutral	N	0.40419137	None	None	N
K/F	0.7055	likely_pathogenic	0.6381	pathogenic	-0.39	Destabilizing	0.997	D	0.455	neutral	None	None	None	None	N
K/G	0.3725	ambiguous	0.3401	ambiguous	-0.133	Destabilizing	0.969	D	0.509	neutral	None	None	None	None	N
K/H	0.3367	likely_benign	0.2946	benign	-0.222	Destabilizing	0.997	D	0.461	neutral	None	None	None	None	N
K/I	0.3111	likely_benign	0.2541	benign	0.185	Stabilizing	0.996	D	0.475	neutral	N	0.488471622	None	None	N
K/L	0.316	likely_benign	0.2813	benign	0.185	Stabilizing	0.969	D	0.483	neutral	None	None	None	None	N
K/M	0.2401	likely_benign	0.2179	benign	-0.111	Destabilizing	0.999	D	0.451	neutral	None	None	None	None	N
K/N	0.3199	likely_benign	0.2708	benign	0.001	Stabilizing	0.92	D	0.423	neutral	N	0.513513778	None	None	N
K/P	0.5015	ambiguous	0.4845	ambiguous	0.138	Stabilizing	0.997	D	0.458	neutral	None	None	None	None	N
K/Q	0.125	likely_benign	0.1153	benign	-0.157	Destabilizing	0.92	D	0.454	neutral	N	0.473416595	None	None	N
K/R	0.0913	likely_benign	0.0879	benign	-0.127	Destabilizing	0.92	D	0.441	neutral	N	0.476302184	None	None	N
K/S	0.3157	likely_benign	0.2793	benign	-0.362	Destabilizing	0.939	D	0.421	neutral	None	None	None	None	N
K/T	0.1561	likely_benign	0.1376	benign	-0.275	Destabilizing	0.959	D	0.481	neutral	N	0.490175559	None	None	N
K/V	0.2642	likely_benign	0.2276	benign	0.138	Stabilizing	0.969	D	0.48	neutral	None	None	None	None	N
K/W	0.7574	likely_pathogenic	0.7287	pathogenic	-0.489	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	N
K/Y	0.6167	likely_pathogenic	0.5518	ambiguous	-0.141	Destabilizing	0.997	D	0.473	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.