TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28177	84754;84755;84756	chr2:178561603;178561602;178561601	chr2:179426330;179426329;179426328
N2AB	26536	79831;79832;79833	chr2:178561603;178561602;178561601	chr2:179426330;179426329;179426328
N2A	25609	77050;77051;77052	chr2:178561603;178561602;178561601	chr2:179426330;179426329;179426328
N2B	19112	57559;57560;57561	chr2:178561603;178561602;178561601	chr2:179426330;179426329;179426328
Novex-1	19237	57934;57935;57936	chr2:178561603;178561602;178561601	chr2:179426330;179426329;179426328
Novex-2	19304	58135;58136;58137	chr2:178561603;178561602;178561601	chr2:179426330;179426329;179426328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-93
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4945
• 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/A	rs532274400	-1.399	0.001	N	0.113	0.082	0.33835085245	gnomAD-2.1.1	7.17E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	7.84E-06	0
V/A	rs532274400	-1.399	0.001	N	0.113	0.082	0.33835085245	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs532274400	-1.399	0.001	N	0.113	0.082	0.33835085245	gnomAD-4.0.0	2.56442E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.39458E-06	1.34167E-05	0
V/E	rs532274400	-1.184	0.001	N	0.288	0.261	0.386882687439	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92901E-04	None	0	0	0	0	0
V/E	rs532274400	-1.184	0.001	N	0.288	0.261	0.386882687439	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
V/E	rs532274400	-1.184	0.001	N	0.288	0.261	0.386882687439	gnomAD-4.0.0	6.56728E-06	None	None	None	None	I	None	0	0	None	0	1.93349E-04	None	0	0	0	0	0
V/L	None	None	0.029	N	0.255	0.046	0.395441342475	gnomAD-4.0.0	6.84535E-07	None	None	None	None	I	None	0	0	None	0	0	None	1.87484E-05	0	0	0	0
V/M	None	None	0.036	N	0.267	0.069	0.379881503574	gnomAD-4.0.0	6.84535E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99696E-07	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	0.107	likely_benign	0.1037	benign	-1.234	Destabilizing	0.001	N	0.113	neutral	N	0.355033907	None	None	I
V/C	0.6317	likely_pathogenic	0.6011	pathogenic	-1.027	Destabilizing	0.901	D	0.486	neutral	None	None	None	None	I
V/D	0.2238	likely_benign	0.1893	benign	-1.122	Destabilizing	0.209	N	0.405	neutral	None	None	None	None	I
V/E	0.1223	likely_benign	0.1186	benign	-1.107	Destabilizing	0.001	N	0.288	neutral	N	0.331178399	None	None	I
V/F	0.1841	likely_benign	0.1631	benign	-0.894	Destabilizing	0.818	D	0.537	neutral	None	None	None	None	I
V/G	0.1975	likely_benign	0.1806	benign	-1.536	Destabilizing	0.166	N	0.348	neutral	N	0.40962054	None	None	I
V/H	0.4246	ambiguous	0.3815	ambiguous	-0.923	Destabilizing	0.901	D	0.478	neutral	None	None	None	None	I
V/I	0.0751	likely_benign	0.074	benign	-0.507	Destabilizing	0.004	N	0.127	neutral	None	None	None	None	I
V/K	0.1837	likely_benign	0.1799	benign	-1.15	Destabilizing	0.007	N	0.293	neutral	None	None	None	None	I
V/L	0.1395	likely_benign	0.1296	benign	-0.507	Destabilizing	0.029	N	0.255	neutral	N	0.448504215	None	None	I
V/M	0.1071	likely_benign	0.1049	benign	-0.608	Destabilizing	0.036	N	0.267	neutral	N	0.412199486	None	None	I
V/N	0.1906	likely_benign	0.157	benign	-1.027	Destabilizing	0.561	D	0.479	neutral	None	None	None	None	I
V/P	0.1762	likely_benign	0.1716	benign	-0.715	Destabilizing	0.722	D	0.514	neutral	None	None	None	None	I
V/Q	0.1954	likely_benign	0.1826	benign	-1.142	Destabilizing	0.39	N	0.477	neutral	None	None	None	None	I
V/R	0.2249	likely_benign	0.209	benign	-0.652	Destabilizing	0.002	N	0.383	neutral	None	None	None	None	I
V/S	0.1532	likely_benign	0.1351	benign	-1.501	Destabilizing	0.209	N	0.319	neutral	None	None	None	None	I
V/T	0.1306	likely_benign	0.1208	benign	-1.363	Destabilizing	0.345	N	0.29	neutral	None	None	None	None	I
V/W	0.7752	likely_pathogenic	0.7416	pathogenic	-1.052	Destabilizing	0.991	D	0.485	neutral	None	None	None	None	I
V/Y	0.4377	ambiguous	0.3885	ambiguous	-0.764	Destabilizing	0.901	D	0.546	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.