TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13768	41527;41528;41529	chr2:178636425;178636424;178636423	chr2:179501152;179501151;179501150
N2AB	12127	36604;36605;36606	chr2:178636425;178636424;178636423	chr2:179501152;179501151;179501150
N2A	11200	33823;33824;33825	chr2:178636425;178636424;178636423	chr2:179501152;179501151;179501150
N2B	4703	14332;14333;14334	chr2:178636425;178636424;178636423	chr2:179501152;179501151;179501150
Novex-1	4828	14707;14708;14709	chr2:178636425;178636424;178636423	chr2:179501152;179501151;179501150
Novex-2	4895	14908;14909;14910	chr2:178636425;178636424;178636423	chr2:179501152;179501151;179501150
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: Ig-87
• Domain position: 85
• Structural Position: 168
• Q(SASA): 0.1031
• 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	None	None	0.667	N	0.758	0.379	0.449572021084	gnomAD-4.0.0	1.37152E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.802E-06	0	0
T/P	None	None	0.667	D	0.755	0.498	0.460616323599	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
T/S	None	None	0.011	N	0.275	0.155	0.141422826196	gnomAD-4.0.0	6.85761E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00998E-07	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	0.1982	likely_benign	0.2444	benign	-0.808	Destabilizing	0.055	N	0.65	neutral	N	0.518595915	None	None	N
T/C	0.7981	likely_pathogenic	0.8461	pathogenic	-0.489	Destabilizing	0.968	D	0.729	prob.delet.	None	None	None	None	N
T/D	0.795	likely_pathogenic	0.87	pathogenic	0.143	Stabilizing	0.157	N	0.778	deleterious	None	None	None	None	N
T/E	0.5941	likely_pathogenic	0.6942	pathogenic	0.151	Stabilizing	0.157	N	0.773	deleterious	None	None	None	None	N
T/F	0.4953	ambiguous	0.5874	pathogenic	-0.899	Destabilizing	0.89	D	0.797	deleterious	None	None	None	None	N
T/G	0.6463	likely_pathogenic	0.706	pathogenic	-1.066	Destabilizing	0.157	N	0.773	deleterious	None	None	None	None	N
T/H	0.4622	ambiguous	0.5623	ambiguous	-1.265	Destabilizing	0.832	D	0.779	deleterious	None	None	None	None	N
T/I	0.34	likely_benign	0.4161	ambiguous	-0.215	Destabilizing	0.667	D	0.758	deleterious	N	0.51152694	None	None	N
T/K	0.4111	ambiguous	0.4983	ambiguous	-0.557	Destabilizing	0.157	N	0.769	deleterious	None	None	None	None	N
T/L	0.2782	likely_benign	0.3378	benign	-0.215	Destabilizing	0.272	N	0.774	deleterious	None	None	None	None	N
T/M	0.1638	likely_benign	0.1987	benign	-0.056	Destabilizing	0.968	D	0.733	prob.delet.	None	None	None	None	N
T/N	0.2599	likely_benign	0.3652	ambiguous	-0.504	Destabilizing	0.001	N	0.413	neutral	N	0.513078531	None	None	N
T/P	0.5649	likely_pathogenic	0.6638	pathogenic	-0.38	Destabilizing	0.667	D	0.755	deleterious	D	0.596021517	None	None	N
T/Q	0.392	ambiguous	0.4727	ambiguous	-0.617	Destabilizing	0.567	D	0.769	deleterious	None	None	None	None	N
T/R	0.3766	ambiguous	0.4652	ambiguous	-0.371	Destabilizing	0.567	D	0.751	deleterious	None	None	None	None	N
T/S	0.2023	likely_benign	0.2648	benign	-0.838	Destabilizing	0.011	N	0.275	neutral	N	0.456707587	None	None	N
T/V	0.2491	likely_benign	0.2962	benign	-0.38	Destabilizing	0.431	N	0.669	neutral	None	None	None	None	N
T/W	0.8456	likely_pathogenic	0.8929	pathogenic	-0.827	Destabilizing	0.968	D	0.776	deleterious	None	None	None	None	N
T/Y	0.5335	ambiguous	0.6181	pathogenic	-0.583	Destabilizing	0.89	D	0.791	deleterious	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.