TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5629	17110;17111;17112	chr2:178732084;178732083;178732082	chr2:179596811;179596810;179596809
N2AB	5312	16159;16160;16161	chr2:178732084;178732083;178732082	chr2:179596811;179596810;179596809
N2A	4385	13378;13379;13380	chr2:178732084;178732083;178732082	chr2:179596811;179596810;179596809
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-39
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.173
• 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
S/N	rs758096327	-0.574	0.117	N	0.589	0.177	0.26547132957	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
S/N	rs758096327	-0.574	0.117	N	0.589	0.177	0.26547132957	gnomAD-4.0.0	6.40629E-06	None	None	None	None	N	None	0	6.87695E-05	None	0	0	None	0	0	2.8795E-06	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
S/A	0.0833	likely_benign	0.081	benign	-0.967	Destabilizing	0.016	N	0.379	neutral	None	None	None	None	N
S/C	0.0961	likely_benign	0.1021	benign	-0.859	Destabilizing	None	N	0.342	neutral	N	0.441610821	None	None	N
S/D	0.6923	likely_pathogenic	0.8397	pathogenic	-1.529	Destabilizing	0.149	N	0.603	neutral	None	None	None	None	N
S/E	0.8101	likely_pathogenic	0.8983	pathogenic	-1.367	Destabilizing	0.149	N	0.644	neutral	None	None	None	None	N
S/F	0.4776	ambiguous	0.5051	ambiguous	-0.887	Destabilizing	0.555	D	0.766	deleterious	None	None	None	None	N
S/G	0.0742	likely_benign	0.1136	benign	-1.325	Destabilizing	None	N	0.135	neutral	N	0.454348044	None	None	N
S/H	0.615	likely_pathogenic	0.744	pathogenic	-1.645	Destabilizing	0.935	D	0.725	prob.delet.	None	None	None	None	N
S/I	0.2368	likely_benign	0.2969	benign	-0.07	Destabilizing	0.317	N	0.785	deleterious	N	0.445456415	None	None	N
S/K	0.8771	likely_pathogenic	0.9483	pathogenic	-0.453	Destabilizing	0.149	N	0.623	neutral	None	None	None	None	N
S/L	0.2034	likely_benign	0.208	benign	-0.07	Destabilizing	0.081	N	0.685	prob.neutral	None	None	None	None	N
S/M	0.3136	likely_benign	0.3434	ambiguous	-0.074	Destabilizing	0.791	D	0.727	prob.delet.	None	None	None	None	N
S/N	0.2554	likely_benign	0.3685	ambiguous	-1.071	Destabilizing	0.117	N	0.589	neutral	N	0.483415059	None	None	N
S/P	0.8226	likely_pathogenic	0.8772	pathogenic	-0.336	Destabilizing	0.555	D	0.78	deleterious	None	None	None	None	N
S/Q	0.7316	likely_pathogenic	0.8392	pathogenic	-0.943	Destabilizing	0.555	D	0.69	prob.neutral	None	None	None	None	N
S/R	0.7918	likely_pathogenic	0.893	pathogenic	-0.694	Destabilizing	0.484	N	0.777	deleterious	D	0.529768523	None	None	N
S/T	0.101	likely_benign	0.1033	benign	-0.787	Destabilizing	0.002	N	0.168	neutral	N	0.401590995	None	None	N
S/V	0.2243	likely_benign	0.2422	benign	-0.336	Destabilizing	0.081	N	0.71	prob.delet.	None	None	None	None	N
S/W	0.63	likely_pathogenic	0.7253	pathogenic	-1.067	Destabilizing	0.935	D	0.743	deleterious	None	None	None	None	N
S/Y	0.4316	ambiguous	0.4908	ambiguous	-0.658	Destabilizing	0.791	D	0.76	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.