TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21528	64807;64808;64809	chr2:178585162;178585161;178585160	chr2:179449889;179449888;179449887
N2AB	19887	59884;59885;59886	chr2:178585162;178585161;178585160	chr2:179449889;179449888;179449887
N2A	18960	57103;57104;57105	chr2:178585162;178585161;178585160	chr2:179449889;179449888;179449887
N2B	12463	37612;37613;37614	chr2:178585162;178585161;178585160	chr2:179449889;179449888;179449887
Novex-1	12588	37987;37988;37989	chr2:178585162;178585161;178585160	chr2:179449889;179449888;179449887
Novex-2	12655	38188;38189;38190	chr2:178585162;178585161;178585160	chr2:179449889;179449888;179449887
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-124
• Domain position: 60
• Structural Position: 143
• Q(SASA): 0.3621
• 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/N	rs2048653243	None	0.733	N	0.263	0.234	0.107399877778	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs2048653243	None	0.733	N	0.263	0.234	0.107399877778	gnomAD-4.0.0	5.12722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.57887E-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
D/A	0.4157	ambiguous	0.358	ambiguous	-0.383	Destabilizing	0.994	D	0.551	neutral	N	0.489014326	None	None	N
D/C	0.8926	likely_pathogenic	0.8443	pathogenic	-0.026	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
D/E	0.2345	likely_benign	0.2057	benign	-0.532	Destabilizing	0.989	D	0.382	neutral	N	0.471177926	None	None	N
D/F	0.8538	likely_pathogenic	0.8191	pathogenic	-0.358	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
D/G	0.3029	likely_benign	0.2648	benign	-0.641	Destabilizing	0.989	D	0.463	neutral	N	0.473140796	None	None	N
D/H	0.5736	likely_pathogenic	0.4927	ambiguous	-0.563	Destabilizing	0.595	D	0.362	neutral	N	0.48253107	None	None	N
D/I	0.8012	likely_pathogenic	0.7485	pathogenic	0.266	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
D/K	0.7135	likely_pathogenic	0.649	pathogenic	-0.178	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	N
D/L	0.7705	likely_pathogenic	0.7195	pathogenic	0.266	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
D/M	0.8583	likely_pathogenic	0.8131	pathogenic	0.609	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/N	0.148	likely_benign	0.1363	benign	-0.392	Destabilizing	0.733	D	0.263	neutral	N	0.411761476	None	None	N
D/P	0.9644	likely_pathogenic	0.9448	pathogenic	0.074	Stabilizing	1.0	D	0.571	neutral	None	None	None	None	N
D/Q	0.6301	likely_pathogenic	0.5616	ambiguous	-0.325	Destabilizing	0.999	D	0.515	neutral	None	None	None	None	N
D/R	0.7554	likely_pathogenic	0.69	pathogenic	-0.056	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
D/S	0.3016	likely_benign	0.254	benign	-0.563	Destabilizing	0.992	D	0.431	neutral	None	None	None	None	N
D/T	0.5309	ambiguous	0.4495	ambiguous	-0.37	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
D/V	0.5926	likely_pathogenic	0.5264	ambiguous	0.074	Stabilizing	0.999	D	0.721	prob.delet.	N	0.466380537	None	None	N
D/W	0.962	likely_pathogenic	0.9436	pathogenic	-0.28	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
D/Y	0.4486	ambiguous	0.3888	ambiguous	-0.161	Destabilizing	0.997	D	0.729	prob.delet.	N	0.461354108	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.