TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28018	84277;84278;84279	chr2:178562080;178562079;178562078	chr2:179426807;179426806;179426805
N2AB	26377	79354;79355;79356	chr2:178562080;178562079;178562078	chr2:179426807;179426806;179426805
N2A	25450	76573;76574;76575	chr2:178562080;178562079;178562078	chr2:179426807;179426806;179426805
N2B	18953	57082;57083;57084	chr2:178562080;178562079;178562078	chr2:179426807;179426806;179426805
Novex-1	19078	57457;57458;57459	chr2:178562080;178562079;178562078	chr2:179426807;179426806;179426805
Novex-2	19145	57658;57659;57660	chr2:178562080;178562079;178562078	chr2:179426807;179426806;179426805
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-142
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1344
• 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
T/A	None	None	0.309	N	0.617	0.152	0.152612264143	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
T/A	0.1236	likely_benign	0.1248	benign	-1.371	Destabilizing	0.309	N	0.617	neutral	N	0.511464324	None	None	N
T/C	0.4842	ambiguous	0.4759	ambiguous	-1.088	Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
T/D	0.936	likely_pathogenic	0.9505	pathogenic	-1.77	Destabilizing	0.742	D	0.735	prob.delet.	None	None	None	None	N
T/E	0.9443	likely_pathogenic	0.9556	pathogenic	-1.502	Destabilizing	0.59	D	0.731	prob.delet.	None	None	None	None	N
T/F	0.7175	likely_pathogenic	0.7515	pathogenic	-1.217	Destabilizing	0.984	D	0.781	deleterious	None	None	None	None	N
T/G	0.5719	likely_pathogenic	0.5909	pathogenic	-1.804	Destabilizing	0.742	D	0.728	prob.delet.	None	None	None	None	N
T/H	0.8241	likely_pathogenic	0.8429	pathogenic	-1.882	Destabilizing	0.987	D	0.766	deleterious	None	None	None	None	N
T/I	0.4524	ambiguous	0.4958	ambiguous	-0.2	Destabilizing	0.939	D	0.772	deleterious	N	0.46654144	None	None	N
T/K	0.9345	likely_pathogenic	0.9437	pathogenic	-0.214	Destabilizing	0.007	N	0.566	neutral	N	0.472163754	None	None	N
T/L	0.2746	likely_benign	0.299	benign	-0.2	Destabilizing	0.742	D	0.73	prob.delet.	None	None	None	None	N
T/M	0.22	likely_benign	0.2403	benign	-0.351	Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	N
T/N	0.6182	likely_pathogenic	0.6588	pathogenic	-1.179	Destabilizing	0.742	D	0.709	prob.delet.	None	None	None	None	N
T/P	0.8523	likely_pathogenic	0.9049	pathogenic	-0.563	Destabilizing	0.939	D	0.774	deleterious	N	0.472163754	None	None	N
T/Q	0.8549	likely_pathogenic	0.8748	pathogenic	-0.828	Destabilizing	0.91	D	0.772	deleterious	None	None	None	None	N
T/R	0.9027	likely_pathogenic	0.9226	pathogenic	-0.642	Destabilizing	0.521	D	0.755	deleterious	N	0.46654144	None	None	N
T/S	0.2009	likely_benign	0.2116	benign	-1.435	Destabilizing	0.034	N	0.379	neutral	N	0.427981723	None	None	N
T/V	0.2813	likely_benign	0.305	benign	-0.563	Destabilizing	0.742	D	0.709	prob.delet.	None	None	None	None	N
T/W	0.9558	likely_pathogenic	0.964	pathogenic	-1.366	Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	N
T/Y	0.8235	likely_pathogenic	0.843	pathogenic	-0.947	Destabilizing	0.984	D	0.779	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.