TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26013	78262;78263;78264	chr2:178568095;178568094;178568093	chr2:179432822;179432821;179432820
N2AB	24372	73339;73340;73341	chr2:178568095;178568094;178568093	chr2:179432822;179432821;179432820
N2A	23445	70558;70559;70560	chr2:178568095;178568094;178568093	chr2:179432822;179432821;179432820
N2B	16948	51067;51068;51069	chr2:178568095;178568094;178568093	chr2:179432822;179432821;179432820
Novex-1	17073	51442;51443;51444	chr2:178568095;178568094;178568093	chr2:179432822;179432821;179432820
Novex-2	17140	51643;51644;51645	chr2:178568095;178568094;178568093	chr2:179432822;179432821;179432820
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-77
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4334
• 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
E/D	rs755117644	-1.051	0.822	N	0.572	0.113	0.191931220699	gnomAD-2.1.1	2.42E-05	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	4.46E-05	0
E/D	rs755117644	-1.051	0.822	N	0.572	0.113	0.191931220699	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	2.41E-05	6.55E-05	0	0	0	None	0	0	7.35E-05	0	0
E/D	rs755117644	-1.051	0.822	N	0.572	0.113	0.191931220699	gnomAD-4.0.0	4.64872E-05	None	None	None	None	I	None	4.00545E-05	3.336E-05	None	0	0	None	0	0	5.67982E-05	0	4.80538E-05

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
E/A	0.1754	likely_benign	0.1858	benign	-0.238	Destabilizing	0.698	D	0.629	neutral	N	0.43545756	None	None	I
E/C	0.8814	likely_pathogenic	0.8799	pathogenic	-0.403	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	I
E/D	0.3336	likely_benign	0.3135	benign	-0.816	Destabilizing	0.822	D	0.572	neutral	N	0.517500154	None	None	I
E/F	0.8829	likely_pathogenic	0.8865	pathogenic	0.373	Stabilizing	0.993	D	0.742	deleterious	None	None	None	None	I
E/G	0.3939	ambiguous	0.3956	ambiguous	-0.544	Destabilizing	0.822	D	0.643	neutral	N	0.506205725	None	None	I
E/H	0.6895	likely_pathogenic	0.7037	pathogenic	0.589	Stabilizing	0.978	D	0.565	neutral	None	None	None	None	I
E/I	0.3246	likely_benign	0.3304	benign	0.575	Stabilizing	0.978	D	0.742	deleterious	None	None	None	None	I
E/K	0.1677	likely_benign	0.1817	benign	-0.048	Destabilizing	0.002	N	0.205	neutral	N	0.453526033	None	None	I
E/L	0.4331	ambiguous	0.4577	ambiguous	0.575	Stabilizing	0.86	D	0.665	neutral	None	None	None	None	I
E/M	0.487	ambiguous	0.5138	ambiguous	0.472	Stabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	I
E/N	0.5347	ambiguous	0.5328	ambiguous	-0.621	Destabilizing	0.86	D	0.552	neutral	None	None	None	None	I
E/P	0.3838	ambiguous	0.3996	ambiguous	0.325	Stabilizing	0.978	D	0.674	neutral	None	None	None	None	I
E/Q	0.1701	likely_benign	0.177	benign	-0.473	Destabilizing	0.822	D	0.571	neutral	N	0.494892653	None	None	I
E/R	0.3387	likely_benign	0.3701	ambiguous	0.37	Stabilizing	0.754	D	0.537	neutral	None	None	None	None	I
E/S	0.3516	ambiguous	0.3558	ambiguous	-0.828	Destabilizing	0.86	D	0.55	neutral	None	None	None	None	I
E/T	0.3154	likely_benign	0.3243	benign	-0.556	Destabilizing	0.86	D	0.643	neutral	None	None	None	None	I
E/V	0.2056	likely_benign	0.2066	benign	0.325	Stabilizing	0.942	D	0.66	neutral	N	0.502530701	None	None	I
E/W	0.9788	likely_pathogenic	0.9798	pathogenic	0.581	Stabilizing	0.998	D	0.743	deleterious	None	None	None	None	I
E/Y	0.8228	likely_pathogenic	0.8301	pathogenic	0.637	Stabilizing	0.993	D	0.733	prob.delet.	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.