TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31810	95653;95654;95655	chr2:178545682;178545681;178545680	chr2:179410409;179410408;179410407
N2AB	30169	90730;90731;90732	chr2:178545682;178545681;178545680	chr2:179410409;179410408;179410407
N2A	29242	87949;87950;87951	chr2:178545682;178545681;178545680	chr2:179410409;179410408;179410407
N2B	22745	68458;68459;68460	chr2:178545682;178545681;178545680	chr2:179410409;179410408;179410407
Novex-1	22870	68833;68834;68835	chr2:178545682;178545681;178545680	chr2:179410409;179410408;179410407
Novex-2	22937	69034;69035;69036	chr2:178545682;178545681;178545680	chr2:179410409;179410408;179410407
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-120
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2545
• 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
P/T	None	None	0.117	N	0.668	0.349	0.326074293725	gnomAD-4.0.0	1.59393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43377E-05	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
P/A	0.0526	likely_benign	0.0541	benign	-1.26	Destabilizing	0.001	N	0.383	neutral	N	0.445114407	None	None	N
P/C	0.2646	likely_benign	0.2692	benign	-1.16	Destabilizing	0.935	D	0.808	deleterious	None	None	None	None	N
P/D	0.5954	likely_pathogenic	0.5616	ambiguous	-1.804	Destabilizing	0.149	N	0.67	neutral	None	None	None	None	N
P/E	0.2017	likely_benign	0.1842	benign	-1.864	Destabilizing	0.035	N	0.545	neutral	None	None	None	None	N
P/F	0.4249	ambiguous	0.4268	ambiguous	-1.406	Destabilizing	0.791	D	0.807	deleterious	None	None	None	None	N
P/G	0.2737	likely_benign	0.2584	benign	-1.474	Destabilizing	0.067	N	0.659	neutral	None	None	None	None	N
P/H	0.1703	likely_benign	0.1618	benign	-0.966	Destabilizing	0.38	N	0.794	deleterious	None	None	None	None	N
P/I	0.2464	likely_benign	0.246	benign	-0.793	Destabilizing	0.555	D	0.792	deleterious	None	None	None	None	N
P/K	0.1475	likely_benign	0.1372	benign	-0.94	Destabilizing	0.035	N	0.625	neutral	None	None	None	None	N
P/L	0.123	likely_benign	0.1148	benign	-0.793	Destabilizing	0.117	N	0.721	prob.delet.	N	0.521343591	None	None	N
P/M	0.2278	likely_benign	0.2203	benign	-0.594	Destabilizing	0.555	D	0.798	deleterious	None	None	None	None	N
P/N	0.3721	ambiguous	0.3512	ambiguous	-0.841	Destabilizing	0.149	N	0.75	deleterious	None	None	None	None	N
P/Q	0.0719	likely_benign	0.0656	benign	-1.181	Destabilizing	None	N	0.392	neutral	N	0.490108604	None	None	N
P/R	0.1056	likely_benign	0.099	benign	-0.358	Destabilizing	0.062	N	0.736	prob.delet.	N	0.501971888	None	None	N
P/S	0.1029	likely_benign	0.1006	benign	-1.222	Destabilizing	0.027	N	0.613	neutral	N	0.477182136	None	None	N
P/T	0.1179	likely_benign	0.1144	benign	-1.191	Destabilizing	0.117	N	0.668	neutral	N	0.509480307	None	None	N
P/V	0.1619	likely_benign	0.1614	benign	-0.917	Destabilizing	0.149	N	0.719	prob.delet.	None	None	None	None	N
P/W	0.5747	likely_pathogenic	0.5572	ambiguous	-1.5	Destabilizing	0.935	D	0.809	deleterious	None	None	None	None	N
P/Y	0.3976	ambiguous	0.3836	ambiguous	-1.164	Destabilizing	0.555	D	0.805	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.