TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31353	94282;94283;94284	chr2:178547569;178547568;178547567	chr2:179412296;179412295;179412294
N2AB	29712	89359;89360;89361	chr2:178547569;178547568;178547567	chr2:179412296;179412295;179412294
N2A	28785	86578;86579;86580	chr2:178547569;178547568;178547567	chr2:179412296;179412295;179412294
N2B	22288	67087;67088;67089	chr2:178547569;178547568;178547567	chr2:179412296;179412295;179412294
Novex-1	22413	67462;67463;67464	chr2:178547569;178547568;178547567	chr2:179412296;179412295;179412294
Novex-2	22480	67663;67664;67665	chr2:178547569;178547568;178547567	chr2:179412296;179412295;179412294
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-116
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.3884
• 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/A	None	None	0.027	N	0.32	0.083	0.203808441222	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.1089	likely_benign	0.1006	benign	-0.401	Destabilizing	0.027	N	0.32	neutral	N	0.461761514	None	None	N
T/C	0.4537	ambiguous	0.4116	ambiguous	-0.183	Destabilizing	0.935	D	0.362	neutral	None	None	None	None	N
T/D	0.5267	ambiguous	0.4669	ambiguous	0.074	Stabilizing	0.149	N	0.321	neutral	None	None	None	None	N
T/E	0.4721	ambiguous	0.4286	ambiguous	-0.021	Destabilizing	0.081	N	0.286	neutral	None	None	None	None	N
T/F	0.4336	ambiguous	0.398	ambiguous	-0.983	Destabilizing	0.791	D	0.435	neutral	None	None	None	None	N
T/G	0.2215	likely_benign	0.1902	benign	-0.492	Destabilizing	0.149	N	0.313	neutral	None	None	None	None	N
T/H	0.3298	likely_benign	0.2763	benign	-0.839	Destabilizing	0.824	D	0.435	neutral	None	None	None	None	N
T/I	0.4522	ambiguous	0.4055	ambiguous	-0.279	Destabilizing	0.484	N	0.331	neutral	N	0.468459177	None	None	N
T/K	0.2807	likely_benign	0.2347	benign	-0.292	Destabilizing	None	N	0.279	neutral	N	0.420048178	None	None	N
T/L	0.1611	likely_benign	0.1499	benign	-0.279	Destabilizing	0.149	N	0.283	neutral	None	None	None	None	N
T/M	0.1183	likely_benign	0.12	benign	0.038	Stabilizing	0.935	D	0.339	neutral	None	None	None	None	N
T/N	0.134	likely_benign	0.1231	benign	-0.005	Destabilizing	0.149	N	0.284	neutral	None	None	None	None	N
T/P	0.5108	ambiguous	0.4738	ambiguous	-0.294	Destabilizing	0.484	N	0.331	neutral	N	0.486774602	None	None	N
T/Q	0.2658	likely_benign	0.2255	benign	-0.308	Destabilizing	0.235	N	0.331	neutral	None	None	None	None	N
T/R	0.2603	likely_benign	0.2212	benign	-0.011	Destabilizing	0.062	N	0.32	neutral	N	0.416143868	None	None	N
T/S	0.0934	likely_benign	0.0864	benign	-0.214	Destabilizing	0.002	N	0.178	neutral	N	0.383530017	None	None	N
T/V	0.2928	likely_benign	0.2596	benign	-0.294	Destabilizing	0.149	N	0.258	neutral	None	None	None	None	N
T/W	0.7493	likely_pathogenic	0.7167	pathogenic	-0.967	Destabilizing	0.935	D	0.527	neutral	None	None	None	None	N
T/Y	0.4601	ambiguous	0.3896	ambiguous	-0.685	Destabilizing	0.791	D	0.437	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.