TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7839	23740;23741;23742	chr2:178720127;178720126;178720125	chr2:179584854;179584853;179584852
N2AB	7522	22789;22790;22791	chr2:178720127;178720126;178720125	chr2:179584854;179584853;179584852
N2A	6595	20008;20009;20010	chr2:178720127;178720126;178720125	chr2:179584854;179584853;179584852
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-63
• Domain position: 45
• Structural Position: 73
• Q(SASA): 0.2046
• 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/R	None	None	None	N	0.233	0.252	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1346	likely_benign	0.1283	benign	-0.255	Destabilizing	None	N	0.275	neutral	None	None	None	None	N
S/C	0.2968	likely_benign	0.271	benign	-0.18	Destabilizing	0.358	N	0.328	neutral	N	0.501351734	None	None	N
S/D	0.3388	likely_benign	0.3161	benign	-0.121	Destabilizing	0.027	N	0.324	neutral	None	None	None	None	N
S/E	0.6764	likely_pathogenic	0.6294	pathogenic	-0.23	Destabilizing	0.037	N	0.31	neutral	None	None	None	None	N
S/F	0.4783	ambiguous	0.4131	ambiguous	-0.898	Destabilizing	0.423	N	0.399	neutral	None	None	None	None	N
S/G	0.0989	likely_benign	0.0963	benign	-0.342	Destabilizing	None	N	0.139	neutral	N	0.494169429	None	None	N
S/H	0.5814	likely_pathogenic	0.5389	ambiguous	-0.858	Destabilizing	0.69	D	0.325	neutral	None	None	None	None	N
S/I	0.527	ambiguous	0.4892	ambiguous	-0.156	Destabilizing	0.12	N	0.416	neutral	N	0.505871185	None	None	N
S/K	0.828	likely_pathogenic	0.8001	pathogenic	-0.497	Destabilizing	0.021	N	0.319	neutral	None	None	None	None	N
S/L	0.2114	likely_benign	0.1861	benign	-0.156	Destabilizing	0.049	N	0.373	neutral	None	None	None	None	N
S/M	0.3606	ambiguous	0.3228	benign	0.126	Stabilizing	0.423	N	0.324	neutral	None	None	None	None	N
S/N	0.157	likely_benign	0.1452	benign	-0.164	Destabilizing	0.002	N	0.369	neutral	N	0.464810375	None	None	N
S/P	0.8597	likely_pathogenic	0.8284	pathogenic	-0.162	Destabilizing	None	N	0.186	neutral	None	None	None	None	N
S/Q	0.727	likely_pathogenic	0.6936	pathogenic	-0.461	Destabilizing	0.265	N	0.367	neutral	None	None	None	None	N
S/R	0.7915	likely_pathogenic	0.7603	pathogenic	-0.236	Destabilizing	None	N	0.233	neutral	N	0.496463435	None	None	N
S/T	0.1065	likely_benign	0.1019	benign	-0.257	Destabilizing	None	N	0.172	neutral	N	0.474129218	None	None	N
S/V	0.4592	ambiguous	0.4383	ambiguous	-0.162	Destabilizing	0.019	N	0.369	neutral	None	None	None	None	N
S/W	0.6027	likely_pathogenic	0.5402	ambiguous	-0.934	Destabilizing	0.894	D	0.463	neutral	None	None	None	None	N
S/Y	0.4134	ambiguous	0.3498	ambiguous	-0.649	Destabilizing	0.423	N	0.397	neutral	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.