TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7848	23767;23768;23769	chr2:178720100;178720099;178720098	chr2:179584827;179584826;179584825
N2AB	7531	22816;22817;22818	chr2:178720100;178720099;178720098	chr2:179584827;179584826;179584825
N2A	6604	20035;20036;20037	chr2:178720100;178720099;178720098	chr2:179584827;179584826;179584825
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-63
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.778
• 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/G	None	None	0.201	N	0.311	0.197	0.159798565429	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	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	0.2758	likely_benign	0.2653	benign	-0.13	Destabilizing	0.016	N	0.225	neutral	N	0.506175934	None	None	I
D/C	0.7422	likely_pathogenic	0.7091	pathogenic	-0.341	Destabilizing	0.992	D	0.292	neutral	None	None	None	None	I
D/E	0.1762	likely_benign	0.1541	benign	-0.319	Destabilizing	0.004	N	0.207	neutral	N	0.416882082	None	None	I
D/F	0.8106	likely_pathogenic	0.7842	pathogenic	0.019	Stabilizing	0.972	D	0.27	neutral	None	None	None	None	I
D/G	0.117	likely_benign	0.1265	benign	-0.288	Destabilizing	0.201	N	0.311	neutral	N	0.468364121	None	None	I
D/H	0.2926	likely_benign	0.2961	benign	0.632	Stabilizing	0.896	D	0.248	neutral	N	0.456149868	None	None	I
D/I	0.7943	likely_pathogenic	0.7432	pathogenic	0.234	Stabilizing	0.92	D	0.297	neutral	None	None	None	None	I
D/K	0.3932	ambiguous	0.3725	ambiguous	0.331	Stabilizing	0.447	N	0.316	neutral	None	None	None	None	I
D/L	0.6642	likely_pathogenic	0.633	pathogenic	0.234	Stabilizing	0.617	D	0.343	neutral	None	None	None	None	I
D/M	0.8339	likely_pathogenic	0.8016	pathogenic	-0.005	Destabilizing	0.992	D	0.271	neutral	None	None	None	None	I
D/N	0.0885	likely_benign	0.0902	benign	-0.163	Destabilizing	0.002	N	0.116	neutral	N	0.427733793	None	None	I
D/P	0.8309	likely_pathogenic	0.7922	pathogenic	0.132	Stabilizing	0.92	D	0.286	neutral	None	None	None	None	I
D/Q	0.3367	likely_benign	0.3209	benign	-0.11	Destabilizing	0.739	D	0.255	neutral	None	None	None	None	I
D/R	0.4045	ambiguous	0.3971	ambiguous	0.672	Stabilizing	0.85	D	0.294	neutral	None	None	None	None	I
D/S	0.1415	likely_benign	0.1433	benign	-0.221	Destabilizing	0.25	N	0.261	neutral	None	None	None	None	I
D/T	0.4583	ambiguous	0.4124	ambiguous	-0.08	Destabilizing	0.617	D	0.312	neutral	None	None	None	None	I
D/V	0.6127	likely_pathogenic	0.5642	pathogenic	0.132	Stabilizing	0.549	D	0.342	neutral	N	0.483154893	None	None	I
D/W	0.9073	likely_pathogenic	0.8964	pathogenic	0.141	Stabilizing	0.992	D	0.45	neutral	None	None	None	None	I
D/Y	0.3852	ambiguous	0.3531	ambiguous	0.256	Stabilizing	0.963	D	0.27	neutral	N	0.462417291	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.