TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9472	28639;28640;28641	chr2:178710683;178710682;178710681	chr2:179575410;179575409;179575408
N2AB	9155	27688;27689;27690	chr2:178710683;178710682;178710681	chr2:179575410;179575409;179575408
N2A	8228	24907;24908;24909	chr2:178710683;178710682;178710681	chr2:179575410;179575409;179575408
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-80
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.3007
• 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/G	rs1257120493	-1.884	0.003	None	0.317	0.341	0.6276227268	gnomAD-2.1.1	1.2E-05	None	None	None	None	I	None	0	0	None	0	1.66908E-04	None	0	None	0	0	0
V/G	rs1257120493	-1.884	0.003	None	0.317	0.341	0.6276227268	gnomAD-4.0.0	3.4225E-06	None	None	None	None	I	None	0	0	None	0	1.25951E-04	None	0	0	0	0	0
V/L	None	None	0.029	None	0.255	0.161	0.464784125046	gnomAD-4.0.0	1.20032E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-05	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	0.0918	likely_benign	0.1283	benign	-1.373	Destabilizing	0.08	N	0.22	neutral	None	None	None	None	I
V/C	0.6536	likely_pathogenic	0.7989	pathogenic	-0.993	Destabilizing	0.991	D	0.475	neutral	None	None	None	None	I
V/D	0.1992	likely_benign	0.2957	benign	-1.295	Destabilizing	0.561	D	0.541	neutral	None	None	None	None	I
V/E	0.1623	likely_benign	0.2169	benign	-1.335	Destabilizing	0.326	N	0.487	neutral	None	None	None	None	I
V/F	0.1126	likely_benign	0.1434	benign	-1.182	Destabilizing	0.818	D	0.494	neutral	None	None	None	None	I
V/G	0.1209	likely_benign	0.2046	benign	-1.645	Destabilizing	0.003	N	0.317	neutral	None	None	None	None	I
V/H	0.3553	ambiguous	0.5141	ambiguous	-1.164	Destabilizing	0.901	D	0.518	neutral	None	None	None	None	I
V/I	0.0802	likely_benign	0.0782	benign	-0.745	Destabilizing	0.004	N	0.141	neutral	None	None	None	None	I
V/K	0.2208	likely_benign	0.3428	ambiguous	-1.163	Destabilizing	0.39	N	0.516	neutral	None	None	None	None	I
V/L	0.1534	likely_benign	0.1804	benign	-0.745	Destabilizing	0.029	N	0.255	neutral	None	None	None	None	I
V/M	0.1125	likely_benign	0.109	benign	-0.56	Destabilizing	0.08	N	0.218	neutral	None	None	None	None	I
V/N	0.1249	likely_benign	0.2101	benign	-0.923	Destabilizing	0.561	D	0.577	neutral	None	None	None	None	I
V/P	0.8659	likely_pathogenic	0.9537	pathogenic	-0.919	Destabilizing	0.901	D	0.536	neutral	None	None	None	None	I
V/Q	0.1724	likely_benign	0.2618	benign	-1.163	Destabilizing	0.103	N	0.379	neutral	None	None	None	None	I
V/R	0.1771	likely_benign	0.2879	benign	-0.58	Destabilizing	0.818	D	0.551	neutral	None	None	None	None	I
V/S	0.0766	likely_benign	0.1212	benign	-1.395	Destabilizing	0.007	N	0.244	neutral	None	None	None	None	I
V/T	0.0842	likely_benign	0.1119	benign	-1.333	Destabilizing	0.017	N	0.13	neutral	None	None	None	None	I
V/W	0.6396	likely_pathogenic	0.7788	pathogenic	-1.312	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	I
V/Y	0.3487	ambiguous	0.5192	ambiguous	-1.038	Destabilizing	0.901	D	0.493	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.