TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8372	25339;25340;25341	chr2:178717760;178717759;178717758	chr2:179582487;179582486;179582485
N2AB	8055	24388;24389;24390	chr2:178717760;178717759;178717758	chr2:179582487;179582486;179582485
N2A	7128	21607;21608;21609	chr2:178717760;178717759;178717758	chr2:179582487;179582486;179582485
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-69
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.4419
• 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
T/A	rs762359298	-0.896	None	N	0.156	0.091	0.206339911435	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.66E-05	0	0
T/A	rs762359298	-0.896	None	N	0.156	0.091	0.206339911435	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.21507E-04	0
T/S	rs762359298	-0.681	None	N	0.176	0.074	0.159798565429	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.04E-06	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	0.1138	likely_benign	0.1164	benign	-0.678	Destabilizing	None	N	0.156	neutral	N	0.503678	None	None	I
T/C	0.6928	likely_pathogenic	0.6708	pathogenic	-0.368	Destabilizing	0.753	D	0.403	neutral	None	None	None	None	I
T/D	0.4669	ambiguous	0.4861	ambiguous	0.786	Stabilizing	None	N	0.239	neutral	None	None	None	None	I
T/E	0.3565	ambiguous	0.3704	ambiguous	0.761	Stabilizing	0.063	N	0.387	neutral	None	None	None	None	I
T/F	0.3136	likely_benign	0.3378	benign	-0.988	Destabilizing	0.639	D	0.494	neutral	None	None	None	None	I
T/G	0.3822	ambiguous	0.3801	ambiguous	-0.865	Destabilizing	0.065	N	0.461	neutral	None	None	None	None	I
T/H	0.3001	likely_benign	0.3098	benign	-1.011	Destabilizing	0.573	D	0.477	neutral	None	None	None	None	I
T/I	0.1684	likely_benign	0.1901	benign	-0.288	Destabilizing	None	N	0.25	neutral	N	0.505526226	None	None	I
T/K	0.1659	likely_benign	0.174	benign	-0.199	Destabilizing	0.159	N	0.401	neutral	None	None	None	None	I
T/L	0.1228	likely_benign	0.1301	benign	-0.288	Destabilizing	0.006	N	0.368	neutral	None	None	None	None	I
T/M	0.0997	likely_benign	0.0946	benign	-0.181	Destabilizing	0.017	N	0.36	neutral	None	None	None	None	I
T/N	0.1329	likely_benign	0.1382	benign	-0.088	Destabilizing	None	N	0.205	neutral	N	0.502139204	None	None	I
T/P	0.1269	likely_benign	0.1358	benign	-0.388	Destabilizing	0.058	N	0.419	neutral	N	0.485132311	None	None	I
T/Q	0.2256	likely_benign	0.2317	benign	-0.214	Destabilizing	0.386	N	0.427	neutral	None	None	None	None	I
T/R	0.1543	likely_benign	0.1642	benign	-0.03	Destabilizing	0.335	N	0.431	neutral	None	None	None	None	I
T/S	0.1533	likely_benign	0.1523	benign	-0.48	Destabilizing	None	N	0.176	neutral	N	0.49628788	None	None	I
T/V	0.1583	likely_benign	0.1658	benign	-0.388	Destabilizing	None	N	0.159	neutral	None	None	None	None	I
T/W	0.7138	likely_pathogenic	0.7365	pathogenic	-0.915	Destabilizing	0.976	D	0.491	neutral	None	None	None	None	I
T/Y	0.3306	likely_benign	0.3477	ambiguous	-0.648	Destabilizing	0.782	D	0.487	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.