TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17287	52084;52085;52086	chr2:178609451;178609450;178609449	chr2:179474178;179474177;179474176
N2AB	15646	47161;47162;47163	chr2:178609451;178609450;178609449	chr2:179474178;179474177;179474176
N2A	14719	44380;44381;44382	chr2:178609451;178609450;178609449	chr2:179474178;179474177;179474176
N2B	8222	24889;24890;24891	chr2:178609451;178609450;178609449	chr2:179474178;179474177;179474176
Novex-1	8347	25264;25265;25266	chr2:178609451;178609450;178609449	chr2:179474178;179474177;179474176
Novex-2	8414	25465;25466;25467	chr2:178609451;178609450;178609449	chr2:179474178;179474177;179474176
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-112
• Domain position: 37
• Structural Position: 56
• Q(SASA): 0.0457
• 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
V/L	rs1333508634	-0.057	0.02	N	0.747	0.09	0.266843984389	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.65E-05	None	0	None	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	0.1207	likely_benign	0.1244	benign	-0.736	Destabilizing	0.104	N	0.743	deleterious	N	0.483494728	None	None	N
V/C	0.4579	ambiguous	0.514	ambiguous	-0.727	Destabilizing	0.968	D	0.829	deleterious	None	None	None	None	N
V/D	0.2051	likely_benign	0.1969	benign	-0.468	Destabilizing	0.331	N	0.866	deleterious	N	0.494922444	None	None	N
V/E	0.1669	likely_benign	0.1614	benign	-0.558	Destabilizing	0.011	N	0.661	neutral	None	None	None	None	N
V/F	0.1456	likely_benign	0.1569	benign	-0.784	Destabilizing	0.497	N	0.885	deleterious	N	0.490821345	None	None	N
V/G	0.1887	likely_benign	0.1928	benign	-0.909	Destabilizing	0.667	D	0.865	deleterious	D	0.530499242	None	None	N
V/H	0.3055	likely_benign	0.3412	ambiguous	-0.411	Destabilizing	0.968	D	0.878	deleterious	None	None	None	None	N
V/I	0.0707	likely_benign	0.0732	benign	-0.416	Destabilizing	0.001	N	0.396	neutral	N	0.475088676	None	None	N
V/K	0.1902	likely_benign	0.1998	benign	-0.699	Destabilizing	0.567	D	0.865	deleterious	None	None	None	None	N
V/L	0.1327	likely_benign	0.1431	benign	-0.416	Destabilizing	0.02	N	0.747	deleterious	N	0.473952525	None	None	N
V/M	0.1223	likely_benign	0.1301	benign	-0.445	Destabilizing	0.567	D	0.826	deleterious	None	None	None	None	N
V/N	0.1315	likely_benign	0.1424	benign	-0.483	Destabilizing	0.726	D	0.893	deleterious	None	None	None	None	N
V/P	0.1855	likely_benign	0.186	benign	-0.487	Destabilizing	0.89	D	0.89	deleterious	None	None	None	None	N
V/Q	0.1965	likely_benign	0.2038	benign	-0.708	Destabilizing	0.567	D	0.894	deleterious	None	None	None	None	N
V/R	0.1708	likely_benign	0.1838	benign	-0.145	Destabilizing	0.567	D	0.897	deleterious	None	None	None	None	N
V/S	0.1397	likely_benign	0.1499	benign	-0.867	Destabilizing	0.157	N	0.834	deleterious	None	None	None	None	N
V/T	0.1033	likely_benign	0.1086	benign	-0.856	Destabilizing	0.005	N	0.339	neutral	None	None	None	None	N
V/W	0.6223	likely_pathogenic	0.6596	pathogenic	-0.878	Destabilizing	0.968	D	0.857	deleterious	None	None	None	None	N
V/Y	0.3109	likely_benign	0.3407	ambiguous	-0.596	Destabilizing	0.726	D	0.877	deleterious	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.