TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5736	17431;17432;17433	chr2:178731560;178731559;178731558	chr2:179596287;179596286;179596285
N2AB	5419	16480;16481;16482	chr2:178731560;178731559;178731558	chr2:179596287;179596286;179596285
N2A	4492	13699;13700;13701	chr2:178731560;178731559;178731558	chr2:179596287;179596286;179596285
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-41
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1096
• 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
I/T	rs1473469854	-1.668	0.837	N	0.558	0.241	0.533950601487	gnomAD-2.1.1	7.26E-06	None	None	None	None	N	None	8.29E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs1473469854	-1.668	0.837	N	0.558	0.241	0.533950601487	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs1473469854	-1.668	0.837	N	0.558	0.241	0.533950601487	gnomAD-4.0.0	7.46317E-06	None	None	None	None	N	None	9.37885E-05	0	None	0	0	None	0	1.65289E-04	8.50025E-07	0	4.82501E-05

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
I/A	0.2933	likely_benign	0.244	benign	-2.189	Highly Destabilizing	0.584	D	0.492	neutral	None	None	None	None	N
I/C	0.8774	likely_pathogenic	0.8565	pathogenic	-1.532	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	N
I/D	0.9705	likely_pathogenic	0.9575	pathogenic	-1.986	Destabilizing	0.96	D	0.741	deleterious	None	None	None	None	N
I/E	0.9307	likely_pathogenic	0.8972	pathogenic	-1.815	Destabilizing	0.872	D	0.701	prob.neutral	None	None	None	None	N
I/F	0.4501	ambiguous	0.4614	ambiguous	-1.261	Destabilizing	0.016	N	0.335	neutral	N	0.490147689	None	None	N
I/G	0.8285	likely_pathogenic	0.796	pathogenic	-2.692	Highly Destabilizing	0.872	D	0.653	neutral	None	None	None	None	N
I/H	0.9595	likely_pathogenic	0.9462	pathogenic	-2.053	Highly Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
I/K	0.9273	likely_pathogenic	0.8869	pathogenic	-1.469	Destabilizing	0.872	D	0.701	prob.neutral	None	None	None	None	N
I/L	0.1081	likely_benign	0.1149	benign	-0.773	Destabilizing	0.007	N	0.164	neutral	N	0.405736794	None	None	N
I/M	0.0914	likely_benign	0.0953	benign	-0.789	Destabilizing	0.54	D	0.34	neutral	N	0.480624129	None	None	N
I/N	0.7503	likely_pathogenic	0.6942	pathogenic	-1.612	Destabilizing	0.947	D	0.737	prob.delet.	N	0.457173371	None	None	N
I/P	0.5387	ambiguous	0.4588	ambiguous	-1.221	Destabilizing	0.993	D	0.727	prob.delet.	None	None	None	None	N
I/Q	0.8979	likely_pathogenic	0.8593	pathogenic	-1.557	Destabilizing	0.98	D	0.725	prob.delet.	None	None	None	None	N
I/R	0.8954	likely_pathogenic	0.8398	pathogenic	-1.173	Destabilizing	0.98	D	0.727	prob.delet.	None	None	None	None	N
I/S	0.5932	likely_pathogenic	0.5308	ambiguous	-2.369	Highly Destabilizing	0.166	N	0.61	neutral	N	0.51321655	None	None	N
I/T	0.2384	likely_benign	0.2073	benign	-2.055	Highly Destabilizing	0.837	D	0.558	neutral	N	0.456666392	None	None	N
I/V	0.1142	likely_benign	0.1162	benign	-1.221	Destabilizing	0.028	N	0.173	neutral	N	0.480104054	None	None	N
I/W	0.9578	likely_pathogenic	0.9525	pathogenic	-1.54	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
I/Y	0.9154	likely_pathogenic	0.8962	pathogenic	-1.248	Destabilizing	0.923	D	0.722	prob.delet.	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.