TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21079	63460;63461;63462	chr2:178588172;178588171;178588170	chr2:179452899;179452898;179452897
N2AB	19438	58537;58538;58539	chr2:178588172;178588171;178588170	chr2:179452899;179452898;179452897
N2A	18511	55756;55757;55758	chr2:178588172;178588171;178588170	chr2:179452899;179452898;179452897
N2B	12014	36265;36266;36267	chr2:178588172;178588171;178588170	chr2:179452899;179452898;179452897
Novex-1	12139	36640;36641;36642	chr2:178588172;178588171;178588170	chr2:179452899;179452898;179452897
Novex-2	12206	36841;36842;36843	chr2:178588172;178588171;178588170	chr2:179452899;179452898;179452897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-41
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.6238
• 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
H/R	rs2049447997	None	0.003	N	0.179	0.078	0.0297737177859	gnomAD-4.0.0	8.40239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18768E-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
H/A	0.139	likely_benign	0.1458	benign	-0.334	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
H/C	0.1322	likely_benign	0.143	benign	0.239	Stabilizing	0.132	N	0.347	neutral	None	None	None	None	N
H/D	0.097	likely_benign	0.1186	benign	0.085	Stabilizing	0.001	N	0.189	neutral	N	0.387607685	None	None	N
H/E	0.1887	likely_benign	0.2045	benign	0.111	Stabilizing	0.001	N	0.127	neutral	None	None	None	None	N
H/F	0.261	likely_benign	0.2552	benign	0.127	Stabilizing	0.041	N	0.361	neutral	None	None	None	None	N
H/G	0.1523	likely_benign	0.153	benign	-0.616	Destabilizing	0.001	N	0.241	neutral	None	None	None	None	N
H/I	0.2994	likely_benign	0.3266	benign	0.39	Stabilizing	0.004	N	0.291	neutral	None	None	None	None	N
H/K	0.1401	likely_benign	0.1477	benign	-0.248	Destabilizing	0.001	N	0.194	neutral	None	None	None	None	N
H/L	0.1315	likely_benign	0.1345	benign	0.39	Stabilizing	0.001	N	0.266	neutral	N	0.501106549	None	None	N
H/M	0.2853	likely_benign	0.2814	benign	0.349	Stabilizing	0.132	N	0.398	neutral	None	None	None	None	N
H/N	0.0442	likely_benign	0.0509	benign	-0.053	Destabilizing	None	N	0.056	neutral	N	0.361055802	None	None	N
H/P	0.5827	likely_pathogenic	0.6122	pathogenic	0.173	Stabilizing	0.007	N	0.271	neutral	N	0.501279908	None	None	N
H/Q	0.1163	likely_benign	0.1216	benign	0.007	Stabilizing	0.007	N	0.211	neutral	N	0.452544598	None	None	N
H/R	0.0987	likely_benign	0.1056	benign	-0.545	Destabilizing	0.003	N	0.179	neutral	N	0.418181308	None	None	N
H/S	0.0756	likely_benign	0.0788	benign	-0.191	Destabilizing	None	N	0.063	neutral	None	None	None	None	N
H/T	0.0843	likely_benign	0.0846	benign	-0.068	Destabilizing	None	N	0.084	neutral	None	None	None	None	N
H/V	0.2288	likely_benign	0.2382	benign	0.173	Stabilizing	0.002	N	0.264	neutral	None	None	None	None	N
H/W	0.3829	ambiguous	0.3983	ambiguous	0.224	Stabilizing	0.316	N	0.328	neutral	None	None	None	None	N
H/Y	0.0892	likely_benign	0.0966	benign	0.564	Stabilizing	0.013	N	0.223	neutral	N	0.489985479	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.