TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9310	28153;28154;28155	chr2:178711308;178711307;178711306	chr2:179576035;179576034;179576033
N2AB	8993	27202;27203;27204	chr2:178711308;178711307;178711306	chr2:179576035;179576034;179576033
N2A	8066	24421;24422;24423	chr2:178711308;178711307;178711306	chr2:179576035;179576034;179576033
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-79
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2379
• 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	rs200207722	-0.32	0.001	N	0.091	0.057	None	gnomAD-2.1.1	8.58E-05	None	None	None	None	I	None	0	2.84E-05	None	0	0	None	0	None	0	1.79893E-04	0
V/I	rs200207722	-0.32	0.001	N	0.091	0.057	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.4699E-04	0	0
V/I	rs200207722	-0.32	0.001	N	0.091	0.057	None	gnomAD-4.0.0	7.68987E-05	None	None	None	None	I	None	0	3.3379E-05	None	0	0	None	3.12578E-05	0	9.16071E-05	0	1.92234E-04

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	0.1999	likely_benign	0.2217	benign	-1.555	Destabilizing	0.165	N	0.324	neutral	N	0.488978601	None	None	I
V/C	0.7266	likely_pathogenic	0.7592	pathogenic	-0.998	Destabilizing	0.981	D	0.343	neutral	None	None	None	None	I
V/D	0.3955	ambiguous	0.4472	ambiguous	-1.741	Destabilizing	0.773	D	0.481	neutral	D	0.535470688	None	None	I
V/E	0.2797	likely_benign	0.3024	benign	-1.619	Destabilizing	0.818	D	0.428	neutral	None	None	None	None	I
V/F	0.1219	likely_benign	0.1451	benign	-0.943	Destabilizing	0.627	D	0.373	neutral	N	0.519314989	None	None	I
V/G	0.2411	likely_benign	0.2757	benign	-1.995	Destabilizing	0.773	D	0.462	neutral	D	0.52318933	None	None	I
V/H	0.4359	ambiguous	0.4694	ambiguous	-1.705	Destabilizing	0.981	D	0.453	neutral	None	None	None	None	I
V/I	0.0611	likely_benign	0.063	benign	-0.391	Destabilizing	0.001	N	0.091	neutral	N	0.467088055	None	None	I
V/K	0.2309	likely_benign	0.2506	benign	-1.389	Destabilizing	0.818	D	0.423	neutral	None	None	None	None	I
V/L	0.1394	likely_benign	0.1636	benign	-0.391	Destabilizing	0.001	N	0.08	neutral	N	0.505529013	None	None	I
V/M	0.1115	likely_benign	0.1248	benign	-0.323	Destabilizing	0.054	N	0.295	neutral	None	None	None	None	I
V/N	0.2523	likely_benign	0.2726	benign	-1.424	Destabilizing	0.932	D	0.471	neutral	None	None	None	None	I
V/P	0.8529	likely_pathogenic	0.9128	pathogenic	-0.746	Destabilizing	0.932	D	0.443	neutral	None	None	None	None	I
V/Q	0.24	likely_benign	0.2643	benign	-1.402	Destabilizing	0.818	D	0.431	neutral	None	None	None	None	I
V/R	0.1841	likely_benign	0.2034	benign	-1.091	Destabilizing	0.818	D	0.477	neutral	None	None	None	None	I
V/S	0.2152	likely_benign	0.2296	benign	-1.984	Destabilizing	0.563	D	0.428	neutral	None	None	None	None	I
V/T	0.168	likely_benign	0.1751	benign	-1.736	Destabilizing	0.388	N	0.32	neutral	None	None	None	None	I
V/W	0.7071	likely_pathogenic	0.7818	pathogenic	-1.371	Destabilizing	0.981	D	0.516	neutral	None	None	None	None	I
V/Y	0.4357	ambiguous	0.4855	ambiguous	-0.971	Destabilizing	0.818	D	0.373	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.