TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16596	50011;50012;50013	chr2:178612935;178612934;178612933	chr2:179477662;179477661;179477660
N2AB	14955	45088;45089;45090	chr2:178612935;178612934;178612933	chr2:179477662;179477661;179477660
N2A	14028	42307;42308;42309	chr2:178612935;178612934;178612933	chr2:179477662;179477661;179477660
N2B	7531	22816;22817;22818	chr2:178612935;178612934;178612933	chr2:179477662;179477661;179477660
Novex-1	7656	23191;23192;23193	chr2:178612935;178612934;178612933	chr2:179477662;179477661;179477660
Novex-2	7723	23392;23393;23394	chr2:178612935;178612934;178612933	chr2:179477662;179477661;179477660
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: Fn3-8
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9616
• 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/A	rs1353241545	0.317	0.027	N	0.319	0.145	0.270001397563	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
D/A	rs1353241545	0.317	0.027	N	0.319	0.145	0.270001397563	gnomAD-4.0.0	1.5935E-06	None	None	None	None	N	None	0	2.28938E-05	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
D/A	0.137	likely_benign	0.1599	benign	0.069	Stabilizing	0.027	N	0.319	neutral	N	0.479446478	None	None	N
D/C	0.5935	likely_pathogenic	0.6498	pathogenic	-0.106	Destabilizing	0.935	D	0.333	neutral	None	None	None	None	N
D/E	0.0765	likely_benign	0.0763	benign	-0.239	Destabilizing	None	N	0.114	neutral	N	0.43036314	None	None	N
D/F	0.6469	likely_pathogenic	0.7106	pathogenic	-0.05	Destabilizing	0.555	D	0.343	neutral	None	None	None	None	N
D/G	0.1253	likely_benign	0.1531	benign	-0.037	Destabilizing	0.117	N	0.373	neutral	N	0.442605585	None	None	N
D/H	0.2834	likely_benign	0.3515	ambiguous	0.553	Stabilizing	0.484	N	0.371	neutral	N	0.467463933	None	None	N
D/I	0.3647	ambiguous	0.4291	ambiguous	0.278	Stabilizing	0.081	N	0.329	neutral	None	None	None	None	N
D/K	0.2035	likely_benign	0.2751	benign	0.435	Stabilizing	0.081	N	0.353	neutral	None	None	None	None	N
D/L	0.3254	likely_benign	0.3846	ambiguous	0.278	Stabilizing	0.081	N	0.327	neutral	None	None	None	None	N
D/M	0.4707	ambiguous	0.5233	ambiguous	0.065	Stabilizing	0.824	D	0.337	neutral	None	None	None	None	N
D/N	0.0954	likely_benign	0.1064	benign	0.275	Stabilizing	0.002	N	0.316	neutral	N	0.469862917	None	None	N
D/P	0.4461	ambiguous	0.5264	ambiguous	0.227	Stabilizing	0.555	D	0.373	neutral	None	None	None	None	N
D/Q	0.2077	likely_benign	0.251	benign	0.267	Stabilizing	0.081	N	0.323	neutral	None	None	None	None	N
D/R	0.2832	likely_benign	0.3848	ambiguous	0.658	Stabilizing	0.235	N	0.341	neutral	None	None	None	None	N
D/S	0.0941	likely_benign	0.1066	benign	0.152	Stabilizing	0.035	N	0.318	neutral	None	None	None	None	N
D/T	0.1545	likely_benign	0.1748	benign	0.239	Stabilizing	0.002	N	0.363	neutral	None	None	None	None	N
D/V	0.2097	likely_benign	0.251	benign	0.227	Stabilizing	0.002	N	0.411	neutral	N	0.475119502	None	None	N
D/W	0.8279	likely_pathogenic	0.8807	pathogenic	-0.026	Destabilizing	0.935	D	0.413	neutral	None	None	None	None	N
D/Y	0.3265	likely_benign	0.398	ambiguous	0.175	Stabilizing	0.741	D	0.343	neutral	N	0.47141923	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.