TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14215	42868;42869;42870	chr2:178633856;178633855;178633854	chr2:179498583;179498582;179498581
N2AB	12574	37945;37946;37947	chr2:178633856;178633855;178633854	chr2:179498583;179498582;179498581
N2A	11647	35164;35165;35166	chr2:178633856;178633855;178633854	chr2:179498583;179498582;179498581
N2B	5150	15673;15674;15675	chr2:178633856;178633855;178633854	chr2:179498583;179498582;179498581
Novex-1	5275	16048;16049;16050	chr2:178633856;178633855;178633854	chr2:179498583;179498582;179498581
Novex-2	5342	16249;16250;16251	chr2:178633856;178633855;178633854	chr2:179498583;179498582;179498581
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-92
• Domain position: 74
• Structural Position: 158
• Q(SASA): 0.1226
• 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
V/F	None	None	0.998	D	0.819	0.568	0.799399892791	gnomAD-4.0.0	1.59218E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85966E-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
V/A	0.4068	ambiguous	0.3777	ambiguous	-1.824	Destabilizing	0.044	N	0.308	neutral	N	0.420626076	None	None	N
V/C	0.8669	likely_pathogenic	0.872	pathogenic	-1.476	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/D	0.9345	likely_pathogenic	0.9091	pathogenic	-1.811	Destabilizing	0.994	D	0.836	deleterious	D	0.594114673	None	None	N
V/E	0.9304	likely_pathogenic	0.9103	pathogenic	-1.637	Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
V/F	0.5662	likely_pathogenic	0.5047	ambiguous	-1.045	Destabilizing	0.998	D	0.819	deleterious	D	0.569486071	None	None	N
V/G	0.553	ambiguous	0.5229	ambiguous	-2.332	Highly Destabilizing	0.925	D	0.767	deleterious	D	0.634744327	None	None	N
V/H	0.9687	likely_pathogenic	0.9553	pathogenic	-1.91	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/I	0.1582	likely_benign	0.149	benign	-0.446	Destabilizing	0.954	D	0.65	neutral	D	0.564203463	None	None	N
V/K	0.9589	likely_pathogenic	0.9422	pathogenic	-1.609	Destabilizing	0.991	D	0.789	deleterious	None	None	None	None	N
V/L	0.5907	likely_pathogenic	0.5429	ambiguous	-0.446	Destabilizing	0.91	D	0.625	neutral	D	0.525666689	None	None	N
V/M	0.6015	likely_pathogenic	0.5282	ambiguous	-0.495	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
V/N	0.8752	likely_pathogenic	0.8216	pathogenic	-1.767	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/P	0.9791	likely_pathogenic	0.9723	pathogenic	-0.873	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9371	likely_pathogenic	0.9159	pathogenic	-1.655	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
V/R	0.9342	likely_pathogenic	0.9134	pathogenic	-1.376	Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
V/S	0.6907	likely_pathogenic	0.6179	pathogenic	-2.454	Highly Destabilizing	0.942	D	0.746	deleterious	None	None	None	None	N
V/T	0.6403	likely_pathogenic	0.5631	ambiguous	-2.124	Highly Destabilizing	0.97	D	0.675	neutral	None	None	None	None	N
V/W	0.9827	likely_pathogenic	0.9757	pathogenic	-1.423	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/Y	0.9011	likely_pathogenic	0.8902	pathogenic	-1.059	Destabilizing	0.999	D	0.805	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.