TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5034	15325;15326;15327	chr2:178734824;178734823;178734822	chr2:179599551;179599550;179599549
N2AB	4717	14374;14375;14376	chr2:178734824;178734823;178734822	chr2:179599551;179599550;179599549
N2A	3790	11593;11594;11595	chr2:178734824;178734823;178734822	chr2:179599551;179599550;179599549
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-33
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.6348
• 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
N/H	rs1211030254	None	0.001	N	0.234	0.126	0.104622674875	gnomAD-4.0.0	1.27304E-05	None	None	None	None	I	None	0	0	None	0	2.21939E-04	None	0	0	0	0	0
N/S	rs764009823	0.112	0.005	N	0.193	0.077	0.115124310173	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	1.78E-05	1.65893E-04
N/S	rs764009823	0.112	0.005	N	0.193	0.077	0.115124310173	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
N/S	rs764009823	0.112	0.005	N	0.193	0.077	0.115124310173	gnomAD-4.0.0	6.8166E-06	None	None	None	None	I	None	2.66951E-05	3.33411E-05	None	0	0	None	0	0	4.23804E-06	1.09803E-05	1.60102E-05

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
N/A	0.3422	ambiguous	0.2902	benign	-0.095	Destabilizing	0.035	N	0.366	neutral	None	None	None	None	I
N/C	0.5604	ambiguous	0.4795	ambiguous	0.047	Stabilizing	0.935	D	0.379	neutral	None	None	None	None	I
N/D	0.1076	likely_benign	0.1012	benign	0.106	Stabilizing	0.117	N	0.312	neutral	N	0.413511425	None	None	I
N/E	0.4614	ambiguous	0.3871	ambiguous	0.042	Stabilizing	0.081	N	0.283	neutral	None	None	None	None	I
N/F	0.7702	likely_pathogenic	0.7168	pathogenic	-0.72	Destabilizing	0.38	N	0.347	neutral	None	None	None	None	I
N/G	0.2676	likely_benign	0.2407	benign	-0.174	Destabilizing	0.149	N	0.292	neutral	None	None	None	None	I
N/H	0.143	likely_benign	0.1273	benign	-0.161	Destabilizing	0.001	N	0.234	neutral	N	0.440913618	None	None	I
N/I	0.615	likely_pathogenic	0.5399	ambiguous	0.012	Stabilizing	0.317	N	0.363	neutral	N	0.498322353	None	None	I
N/K	0.4204	ambiguous	0.3238	benign	0.099	Stabilizing	None	N	0.203	neutral	N	0.43629383	None	None	I
N/L	0.4986	ambiguous	0.4335	ambiguous	0.012	Stabilizing	0.149	N	0.399	neutral	None	None	None	None	I
N/M	0.6107	likely_pathogenic	0.5416	ambiguous	0.038	Stabilizing	0.935	D	0.322	neutral	None	None	None	None	I
N/P	0.697	likely_pathogenic	0.6799	pathogenic	-0.002	Destabilizing	0.555	D	0.352	neutral	None	None	None	None	I
N/Q	0.4056	ambiguous	0.3401	ambiguous	-0.338	Destabilizing	0.235	N	0.272	neutral	None	None	None	None	I
N/R	0.4662	ambiguous	0.3779	ambiguous	0.17	Stabilizing	0.081	N	0.29	neutral	None	None	None	None	I
N/S	0.0996	likely_benign	0.093	benign	-0.116	Destabilizing	0.005	N	0.193	neutral	N	0.446998603	None	None	I
N/T	0.2872	likely_benign	0.2447	benign	-0.069	Destabilizing	0.002	N	0.221	neutral	N	0.449306925	None	None	I
N/V	0.6126	likely_pathogenic	0.5318	ambiguous	-0.002	Destabilizing	0.38	N	0.391	neutral	None	None	None	None	I
N/W	0.8923	likely_pathogenic	0.8616	pathogenic	-0.863	Destabilizing	0.935	D	0.475	neutral	None	None	None	None	I
N/Y	0.3023	likely_benign	0.2514	benign	-0.531	Destabilizing	0.188	N	0.336	neutral	N	0.498322353	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.