TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27912	83959;83960;83961	chr2:178562398;178562397;178562396	chr2:179427125;179427124;179427123
N2AB	26271	79036;79037;79038	chr2:178562398;178562397;178562396	chr2:179427125;179427124;179427123
N2A	25344	76255;76256;76257	chr2:178562398;178562397;178562396	chr2:179427125;179427124;179427123
N2B	18847	56764;56765;56766	chr2:178562398;178562397;178562396	chr2:179427125;179427124;179427123
Novex-1	18972	57139;57140;57141	chr2:178562398;178562397;178562396	chr2:179427125;179427124;179427123
Novex-2	19039	57340;57341;57342	chr2:178562398;178562397;178562396	chr2:179427125;179427124;179427123
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-91
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4855
• 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
T/I	rs1704019364	None	None	N	0.219	0.116	0.241078983079	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/I	rs1704019364	None	None	N	0.219	0.116	0.241078983079	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	0	6.55136E-05	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
T/A	0.061	likely_benign	0.0629	benign	-0.661	Destabilizing	None	N	0.13	neutral	N	0.455739619	None	None	N
T/C	0.2471	likely_benign	0.2667	benign	-0.309	Destabilizing	0.261	N	0.471	neutral	None	None	None	None	N
T/D	0.3049	likely_benign	0.3562	ambiguous	-0.417	Destabilizing	0.007	N	0.482	neutral	None	None	None	None	N
T/E	0.2361	likely_benign	0.2732	benign	-0.46	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
T/F	0.1262	likely_benign	0.1438	benign	-0.873	Destabilizing	0.151	N	0.588	neutral	None	None	None	None	N
T/G	0.178	likely_benign	0.1909	benign	-0.872	Destabilizing	0.024	N	0.454	neutral	None	None	None	None	N
T/H	0.1895	likely_benign	0.2055	benign	-1.171	Destabilizing	0.322	N	0.515	neutral	None	None	None	None	N
T/I	0.0705	likely_benign	0.0764	benign	-0.201	Destabilizing	None	N	0.219	neutral	N	0.494759367	None	None	N
T/K	0.1912	likely_benign	0.2224	benign	-0.735	Destabilizing	0.014	N	0.479	neutral	None	None	None	None	N
T/L	0.0565	likely_benign	0.0589	benign	-0.201	Destabilizing	None	N	0.185	neutral	None	None	None	None	N
T/M	0.0718	likely_benign	0.0752	benign	0.208	Stabilizing	0.001	N	0.301	neutral	None	None	None	None	N
T/N	0.092	likely_benign	0.1001	benign	-0.532	Destabilizing	0.011	N	0.33	neutral	N	0.50018383	None	None	N
T/P	0.0779	likely_benign	0.0808	benign	-0.324	Destabilizing	0.011	N	0.49	neutral	N	0.462993665	None	None	N
T/Q	0.1796	likely_benign	0.2004	benign	-0.804	Destabilizing	0.015	N	0.536	neutral	None	None	None	None	N
T/R	0.1581	likely_benign	0.1892	benign	-0.371	Destabilizing	0.151	N	0.491	neutral	None	None	None	None	N
T/S	0.0837	likely_benign	0.0888	benign	-0.748	Destabilizing	0.001	N	0.352	neutral	N	0.448773574	None	None	N
T/V	0.0655	likely_benign	0.0687	benign	-0.324	Destabilizing	None	N	0.125	neutral	None	None	None	None	N
T/W	0.4509	ambiguous	0.4999	ambiguous	-0.814	Destabilizing	0.936	D	0.515	neutral	None	None	None	None	N
T/Y	0.1757	likely_benign	0.1991	benign	-0.593	Destabilizing	0.559	D	0.599	neutral	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.