TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8215	24868;24869;24870	chr2:178718463;178718462;178718461	chr2:179583190;179583189;179583188
N2AB	7898	23917;23918;23919	chr2:178718463;178718462;178718461	chr2:179583190;179583189;179583188
N2A	6971	21136;21137;21138	chr2:178718463;178718462;178718461	chr2:179583190;179583189;179583188
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-67
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.291
• 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
E/G	None	None	0.007	N	0.255	0.087	0.0297737177859	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85842E-06	0	0
E/K	rs2077831957	None	0.007	N	0.193	0.05	0.0716867268079	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
E/K	rs2077831957	None	0.007	N	0.193	0.05	0.0716867268079	gnomAD-4.0.0	2.56239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78636E-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
E/A	0.1106	likely_benign	0.1067	benign	None	Stabilizing	None	N	0.144	neutral	N	0.498209812	None	None	N
E/C	0.7282	likely_pathogenic	0.6853	pathogenic	-0.321	Destabilizing	0.245	N	0.363	neutral	None	None	None	None	N
E/D	0.0833	likely_benign	0.088	benign	-0.488	Destabilizing	0.014	N	0.207	neutral	N	0.451570658	None	None	N
E/F	0.5984	likely_pathogenic	0.5471	ambiguous	-0.076	Destabilizing	0.022	N	0.467	neutral	None	None	None	None	N
E/G	0.0913	likely_benign	0.0853	benign	-0.078	Destabilizing	0.007	N	0.255	neutral	N	0.479063904	None	None	N
E/H	0.2316	likely_benign	0.2265	benign	0.553	Stabilizing	None	N	0.188	neutral	None	None	None	None	N
E/I	0.3013	likely_benign	0.2665	benign	0.145	Stabilizing	0.044	N	0.445	neutral	None	None	None	None	N
E/K	0.0818	likely_benign	0.0724	benign	0.284	Stabilizing	0.007	N	0.193	neutral	N	0.504770425	None	None	N
E/L	0.2667	likely_benign	0.2281	benign	0.145	Stabilizing	0.009	N	0.277	neutral	None	None	None	None	N
E/M	0.3757	ambiguous	0.3325	benign	-0.094	Destabilizing	0.245	N	0.359	neutral	None	None	None	None	N
E/N	0.1379	likely_benign	0.1297	benign	0.036	Stabilizing	0.018	N	0.173	neutral	None	None	None	None	N
E/P	0.1098	likely_benign	0.1127	benign	0.112	Stabilizing	None	N	0.144	neutral	None	None	None	None	N
E/Q	0.0874	likely_benign	0.0828	benign	0.045	Stabilizing	None	N	0.149	neutral	N	0.47448759	None	None	N
E/R	0.1303	likely_benign	0.1174	benign	0.473	Stabilizing	None	N	0.165	neutral	None	None	None	None	N
E/S	0.1005	likely_benign	0.1031	benign	-0.067	Destabilizing	None	N	0.162	neutral	None	None	None	None	N
E/T	0.1518	likely_benign	0.1458	benign	0.012	Stabilizing	None	N	0.185	neutral	None	None	None	None	N
E/V	0.1937	likely_benign	0.1756	benign	0.112	Stabilizing	0.007	N	0.32	neutral	N	0.467670757	None	None	N
E/W	0.6969	likely_pathogenic	0.644	pathogenic	-0.065	Destabilizing	0.55	D	0.365	neutral	None	None	None	None	N
E/Y	0.4205	ambiguous	0.3855	ambiguous	0.123	Stabilizing	0.001	N	0.216	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.