TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7338	22237;22238;22239	chr2:178722887;178722886;178722885	chr2:179587614;179587613;179587612
N2AB	7021	21286;21287;21288	chr2:178722887;178722886;178722885	chr2:179587614;179587613;179587612
N2A	6094	18505;18506;18507	chr2:178722887;178722886;178722885	chr2:179587614;179587613;179587612
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-58
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.6096
• Predicted PPI site: I

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/N	rs773799312	0.118	0.801	N	0.397	0.146	0.128392430309	gnomAD-2.1.1	2.43E-05	None	None	None	None	I	None	0	0	None	0	3.37952E-04	None	0	None	0	0	0
D/N	rs773799312	0.118	0.801	N	0.397	0.146	0.128392430309	gnomAD-4.0.0	1.43404E-05	None	None	None	None	I	None	0	0	None	0	2.50153E-04	None	0	0	0	0	0
D/V	rs770976572	0.119	0.669	N	0.423	0.255	0.453588565359	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
D/V	rs770976572	0.119	0.669	N	0.423	0.255	0.453588565359	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.55E-05	0	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	0.2077	likely_benign	0.2928	benign	-0.371	Destabilizing	0.454	N	0.365	neutral	N	0.50679201	None	None	I
D/C	0.708	likely_pathogenic	0.8507	pathogenic	0.131	Stabilizing	0.998	D	0.471	neutral	None	None	None	None	I
D/E	0.17	likely_benign	0.1991	benign	-0.335	Destabilizing	0.669	D	0.381	neutral	N	0.42738429	None	None	I
D/F	0.5908	likely_pathogenic	0.7362	pathogenic	-0.295	Destabilizing	0.949	D	0.441	neutral	None	None	None	None	I
D/G	0.229	likely_benign	0.3337	benign	-0.586	Destabilizing	0.012	N	0.273	neutral	N	0.487704817	None	None	I
D/H	0.3403	ambiguous	0.4481	ambiguous	-0.23	Destabilizing	0.991	D	0.284	neutral	N	0.511083109	None	None	I
D/I	0.4216	ambiguous	0.5751	pathogenic	0.155	Stabilizing	0.904	D	0.443	neutral	None	None	None	None	I
D/K	0.4108	ambiguous	0.5295	ambiguous	0.433	Stabilizing	0.728	D	0.309	neutral	None	None	None	None	I
D/L	0.4602	ambiguous	0.6081	pathogenic	0.155	Stabilizing	0.037	N	0.359	neutral	None	None	None	None	I
D/M	0.6274	likely_pathogenic	0.7561	pathogenic	0.398	Stabilizing	0.986	D	0.429	neutral	None	None	None	None	I
D/N	0.1034	likely_benign	0.1267	benign	0.036	Stabilizing	0.801	D	0.397	neutral	N	0.505367858	None	None	I
D/P	0.9218	likely_pathogenic	0.9618	pathogenic	0.002	Stabilizing	0.974	D	0.292	neutral	None	None	None	None	I
D/Q	0.3406	ambiguous	0.431	ambiguous	0.073	Stabilizing	0.325	N	0.326	neutral	None	None	None	None	I
D/R	0.4679	ambiguous	0.5991	pathogenic	0.529	Stabilizing	0.949	D	0.405	neutral	None	None	None	None	I
D/S	0.1278	likely_benign	0.1672	benign	-0.06	Destabilizing	0.067	N	0.32	neutral	None	None	None	None	I
D/T	0.2832	likely_benign	0.3978	ambiguous	0.115	Stabilizing	0.728	D	0.316	neutral	None	None	None	None	I
D/V	0.2636	likely_benign	0.3723	ambiguous	0.002	Stabilizing	0.669	D	0.423	neutral	N	0.468444452	None	None	I
D/W	0.9172	likely_pathogenic	0.9562	pathogenic	-0.134	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	I
D/Y	0.2479	likely_benign	0.3477	ambiguous	-0.038	Destabilizing	0.989	D	0.439	neutral	N	0.510083031	None	None	I

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.