TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28066	84421;84422;84423	chr2:178561936;178561935;178561934	chr2:179426663;179426662;179426661
N2AB	26425	79498;79499;79500	chr2:178561936;178561935;178561934	chr2:179426663;179426662;179426661
N2A	25498	76717;76718;76719	chr2:178561936;178561935;178561934	chr2:179426663;179426662;179426661
N2B	19001	57226;57227;57228	chr2:178561936;178561935;178561934	chr2:179426663;179426662;179426661
Novex-1	19126	57601;57602;57603	chr2:178561936;178561935;178561934	chr2:179426663;179426662;179426661
Novex-2	19193	57802;57803;57804	chr2:178561936;178561935;178561934	chr2:179426663;179426662;179426661
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-92
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.2206
• 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
E/K	rs1703825463	None	0.822	N	0.512	0.299	0.272205846399	gnomAD-4.0.0	2.05312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69873E-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
E/A	0.18	likely_benign	0.1717	benign	-0.605	Destabilizing	0.822	D	0.503	neutral	N	0.468419497	None	None	N
E/C	0.8524	likely_pathogenic	0.854	pathogenic	-0.148	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
E/D	0.0923	likely_benign	0.0947	benign	-0.54	Destabilizing	0.006	N	0.1	neutral	N	0.463569668	None	None	N
E/F	0.8277	likely_pathogenic	0.8278	pathogenic	-0.383	Destabilizing	0.993	D	0.663	neutral	None	None	None	None	N
E/G	0.2206	likely_benign	0.2059	benign	-0.849	Destabilizing	0.698	D	0.532	neutral	N	0.491069655	None	None	N
E/H	0.4705	ambiguous	0.4765	ambiguous	-0.355	Destabilizing	0.978	D	0.529	neutral	None	None	None	None	N
E/I	0.5705	likely_pathogenic	0.5589	ambiguous	0.023	Stabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	N
E/K	0.2114	likely_benign	0.1908	benign	0.065	Stabilizing	0.822	D	0.512	neutral	N	0.479739803	None	None	N
E/L	0.5963	likely_pathogenic	0.5888	pathogenic	0.023	Stabilizing	0.978	D	0.67	neutral	None	None	None	None	N
E/M	0.5549	ambiguous	0.5543	ambiguous	0.268	Stabilizing	0.998	D	0.619	neutral	None	None	None	None	N
E/N	0.2003	likely_benign	0.2055	benign	-0.315	Destabilizing	0.043	N	0.203	neutral	None	None	None	None	N
E/P	0.9591	likely_pathogenic	0.9532	pathogenic	-0.166	Destabilizing	0.978	D	0.593	neutral	None	None	None	None	N
E/Q	0.1975	likely_benign	0.1902	benign	-0.258	Destabilizing	0.97	D	0.535	neutral	N	0.495210712	None	None	N
E/R	0.3518	ambiguous	0.3309	benign	0.268	Stabilizing	0.956	D	0.539	neutral	None	None	None	None	N
E/S	0.1802	likely_benign	0.1882	benign	-0.5	Destabilizing	0.754	D	0.488	neutral	None	None	None	None	N
E/T	0.2337	likely_benign	0.2418	benign	-0.299	Destabilizing	0.86	D	0.533	neutral	None	None	None	None	N
E/V	0.3745	ambiguous	0.3582	ambiguous	-0.166	Destabilizing	0.97	D	0.629	neutral	N	0.502452414	None	None	N
E/W	0.9321	likely_pathogenic	0.9311	pathogenic	-0.183	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
E/Y	0.6795	likely_pathogenic	0.6765	pathogenic	-0.137	Destabilizing	0.993	D	0.633	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.