TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21109	63550;63551;63552	chr2:178588082;178588081;178588080	chr2:179452809;179452808;179452807
N2AB	19468	58627;58628;58629	chr2:178588082;178588081;178588080	chr2:179452809;179452808;179452807
N2A	18541	55846;55847;55848	chr2:178588082;178588081;178588080	chr2:179452809;179452808;179452807
N2B	12044	36355;36356;36357	chr2:178588082;178588081;178588080	chr2:179452809;179452808;179452807
Novex-1	12169	36730;36731;36732	chr2:178588082;178588081;178588080	chr2:179452809;179452808;179452807
Novex-2	12236	36931;36932;36933	chr2:178588082;178588081;178588080	chr2:179452809;179452808;179452807
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-41
• Domain position: 46
• Structural Position: 56
• Q(SASA): 1.1179
• 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
D/Y	None	None	0.975	N	0.523	0.317	0.529311486226	gnomAD-4.0.0	1.59305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86131E-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
D/A	0.0905	likely_benign	0.0921	benign	0.044	Stabilizing	0.003	N	0.397	neutral	N	0.498258245	None	None	N
D/C	0.3922	ambiguous	0.3832	ambiguous	-0.319	Destabilizing	0.981	D	0.489	neutral	None	None	None	None	N
D/E	0.1022	likely_benign	0.0985	benign	-0.59	Destabilizing	0.139	N	0.487	neutral	N	0.463238808	None	None	N
D/F	0.3744	ambiguous	0.3852	ambiguous	-0.179	Destabilizing	0.893	D	0.533	neutral	None	None	None	None	N
D/G	0.0813	likely_benign	0.0815	benign	-0.008	Destabilizing	0.002	N	0.398	neutral	N	0.443959613	None	None	N
D/H	0.1625	likely_benign	0.1518	benign	0.512	Stabilizing	0.927	D	0.521	neutral	N	0.517710798	None	None	N
D/I	0.2112	likely_benign	0.2128	benign	0.112	Stabilizing	0.543	D	0.591	neutral	None	None	None	None	N
D/K	0.1695	likely_benign	0.1669	benign	0.204	Stabilizing	0.001	N	0.369	neutral	None	None	None	None	N
D/L	0.205	likely_benign	0.2164	benign	0.112	Stabilizing	0.329	N	0.593	neutral	None	None	None	None	N
D/M	0.3571	ambiguous	0.3673	ambiguous	-0.138	Destabilizing	0.085	N	0.55	neutral	None	None	None	None	N
D/N	0.0772	likely_benign	0.0755	benign	0.12	Stabilizing	0.425	N	0.593	neutral	N	0.464274759	None	None	N
D/P	0.2867	likely_benign	0.2989	benign	0.105	Stabilizing	0.828	D	0.619	neutral	None	None	None	None	N
D/Q	0.1797	likely_benign	0.1788	benign	0.076	Stabilizing	0.704	D	0.581	neutral	None	None	None	None	N
D/R	0.2177	likely_benign	0.2157	benign	0.409	Stabilizing	0.007	N	0.457	neutral	None	None	None	None	N
D/S	0.0827	likely_benign	0.0827	benign	0.006	Stabilizing	0.037	N	0.407	neutral	None	None	None	None	N
D/T	0.1207	likely_benign	0.1204	benign	0.053	Stabilizing	0.329	N	0.604	neutral	None	None	None	None	N
D/V	0.127	likely_benign	0.129	benign	0.105	Stabilizing	0.27	N	0.593	neutral	N	0.498258245	None	None	N
D/W	0.6846	likely_pathogenic	0.6918	pathogenic	-0.202	Destabilizing	0.995	D	0.488	neutral	None	None	None	None	N
D/Y	0.1635	likely_benign	0.1607	benign	0.021	Stabilizing	0.975	D	0.523	neutral	N	0.478837523	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.