TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6456	19591;19592;19593	chr2:178728560;178728559;178728558	chr2:179593287;179593286;179593285
N2AB	6139	18640;18641;18642	chr2:178728560;178728559;178728558	chr2:179593287;179593286;179593285
N2A	5212	15859;15860;15861	chr2:178728560;178728559;178728558	chr2:179593287;179593286;179593285
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-48
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1276
• 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/N	None	None	0.642	N	0.539	0.322	0.372087925617	gnomAD-4.0.0	6.84534E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99713E-07	0	0
T/S	None	None	0.01	N	0.211	0.075	0.202949470691	gnomAD-4.0.0	2.0536E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69914E-06	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	0.0951	likely_benign	0.0889	benign	-1.321	Destabilizing	0.139	N	0.357	neutral	N	0.504274569	None	None	N
T/C	0.4518	ambiguous	0.4349	ambiguous	-1.125	Destabilizing	0.981	D	0.676	prob.neutral	None	None	None	None	N
T/D	0.6116	likely_pathogenic	0.5603	ambiguous	-1.765	Destabilizing	0.704	D	0.666	neutral	None	None	None	None	N
T/E	0.404	ambiguous	0.3791	ambiguous	-1.569	Destabilizing	0.704	D	0.647	neutral	None	None	None	None	N
T/F	0.3475	ambiguous	0.3158	benign	-1.068	Destabilizing	0.543	D	0.683	prob.neutral	None	None	None	None	N
T/G	0.3946	ambiguous	0.3722	ambiguous	-1.714	Destabilizing	0.329	N	0.629	neutral	None	None	None	None	N
T/H	0.295	likely_benign	0.2653	benign	-1.797	Destabilizing	0.944	D	0.673	neutral	None	None	None	None	N
T/I	0.1578	likely_benign	0.1673	benign	-0.293	Destabilizing	0.01	N	0.413	neutral	N	0.506736082	None	None	N
T/K	0.2714	likely_benign	0.2369	benign	-0.607	Destabilizing	0.704	D	0.641	neutral	None	None	None	None	N
T/L	0.1482	likely_benign	0.1411	benign	-0.293	Destabilizing	0.031	N	0.559	neutral	None	None	None	None	N
T/M	0.1136	likely_benign	0.1084	benign	-0.321	Destabilizing	0.085	N	0.559	neutral	None	None	None	None	N
T/N	0.1888	likely_benign	0.1749	benign	-1.313	Destabilizing	0.642	D	0.539	neutral	N	0.493767637	None	None	N
T/P	0.8573	likely_pathogenic	0.8268	pathogenic	-0.606	Destabilizing	0.784	D	0.698	prob.neutral	N	0.516898322	None	None	N
T/Q	0.2697	likely_benign	0.2432	benign	-1.149	Destabilizing	0.828	D	0.719	prob.delet.	None	None	None	None	N
T/R	0.1934	likely_benign	0.1622	benign	-0.757	Destabilizing	0.704	D	0.699	prob.neutral	None	None	None	None	N
T/S	0.1224	likely_benign	0.1155	benign	-1.528	Destabilizing	0.01	N	0.211	neutral	N	0.448669213	None	None	N
T/V	0.1335	likely_benign	0.1454	benign	-0.606	Destabilizing	0.004	N	0.131	neutral	None	None	None	None	N
T/W	0.738	likely_pathogenic	0.7015	pathogenic	-1.189	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
T/Y	0.3997	ambiguous	0.3525	ambiguous	-0.811	Destabilizing	0.031	N	0.54	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.