TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8062	24409;24410;24411	chr2:178719206;178719205;178719204	chr2:179583933;179583932;179583931
N2AB	7745	23458;23459;23460	chr2:178719206;178719205;178719204	chr2:179583933;179583932;179583931
N2A	6818	20677;20678;20679	chr2:178719206;178719205;178719204	chr2:179583933;179583932;179583931
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-65
• Domain position: 78
• Structural Position: 162
• Q(SASA): 1.0353
• 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
V/I	rs879134005	-0.081	0.003	N	0.22	0.055	0.156986980423	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs879134005	-0.081	0.003	N	0.22	0.055	0.156986980423	gnomAD-4.0.0	1.59143E-06	None	None	None	None	I	None	5.65675E-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
V/A	0.0952	likely_benign	0.1043	benign	-0.387	Destabilizing	None	N	0.113	neutral	N	0.414288146	None	None	I
V/C	0.6933	likely_pathogenic	0.7336	pathogenic	-0.847	Destabilizing	0.667	D	0.27	neutral	None	None	None	None	I
V/D	0.1873	likely_benign	0.2006	benign	-0.44	Destabilizing	0.124	N	0.277	neutral	None	None	None	None	I
V/E	0.1236	likely_benign	0.1671	benign	-0.561	Destabilizing	0.003	N	0.205	neutral	N	0.401433492	None	None	I
V/F	0.1615	likely_benign	0.147	benign	-0.777	Destabilizing	0.331	N	0.293	neutral	None	None	None	None	I
V/G	0.1709	likely_benign	0.1759	benign	-0.436	Destabilizing	0.096	N	0.281	neutral	N	0.477742192	None	None	I
V/H	0.3667	ambiguous	0.4251	ambiguous	-0.038	Destabilizing	0.859	D	0.211	neutral	None	None	None	None	I
V/I	0.0759	likely_benign	0.0782	benign	-0.398	Destabilizing	0.003	N	0.22	neutral	N	0.485265597	None	None	I
V/K	0.1595	likely_benign	0.2155	benign	-0.441	Destabilizing	0.002	N	0.121	neutral	None	None	None	None	I
V/L	0.1524	likely_benign	0.167	benign	-0.398	Destabilizing	None	N	0.148	neutral	N	0.488420546	None	None	I
V/M	0.1013	likely_benign	0.1134	benign	-0.595	Destabilizing	0.009	N	0.177	neutral	None	None	None	None	I
V/N	0.1806	likely_benign	0.2022	benign	-0.261	Destabilizing	0.22	N	0.27	neutral	None	None	None	None	I
V/P	0.3931	ambiguous	0.4149	ambiguous	-0.367	Destabilizing	0.364	N	0.293	neutral	None	None	None	None	I
V/Q	0.1785	likely_benign	0.2275	benign	-0.484	Destabilizing	0.22	N	0.294	neutral	None	None	None	None	I
V/R	0.1554	likely_benign	0.1854	benign	0.03	Stabilizing	0.124	N	0.278	neutral	None	None	None	None	I
V/S	0.1407	likely_benign	0.1506	benign	-0.556	Destabilizing	0.055	N	0.237	neutral	None	None	None	None	I
V/T	0.1091	likely_benign	0.1234	benign	-0.588	Destabilizing	0.001	N	0.217	neutral	None	None	None	None	I
V/W	0.6952	likely_pathogenic	0.7061	pathogenic	-0.824	Destabilizing	0.958	D	0.221	neutral	None	None	None	None	I
V/Y	0.4189	ambiguous	0.4429	ambiguous	-0.56	Destabilizing	0.667	D	0.271	neutral	None	None	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.