TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29887	89884;89885;89886	chr2:178553241;178553240;178553239	chr2:179417968;179417967;179417966
N2AB	28246	84961;84962;84963	chr2:178553241;178553240;178553239	chr2:179417968;179417967;179417966
N2A	27319	82180;82181;82182	chr2:178553241;178553240;178553239	chr2:179417968;179417967;179417966
N2B	20822	62689;62690;62691	chr2:178553241;178553240;178553239	chr2:179417968;179417967;179417966
Novex-1	20947	63064;63065;63066	chr2:178553241;178553240;178553239	chr2:179417968;179417967;179417966
Novex-2	21014	63265;63266;63267	chr2:178553241;178553240;178553239	chr2:179417968;179417967;179417966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-147
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.3366
• 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/G	None	None	0.012	N	0.281	0.12	0.266843984389	gnomAD-4.0.0	1.59251E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	None	0	0	0	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	0.0793	likely_benign	0.0812	benign	-0.458	Destabilizing	None	N	0.115	neutral	None	None	None	None	N
S/C	0.0785	likely_benign	0.0745	benign	-0.409	Destabilizing	0.56	D	0.477	neutral	D	0.527019006	None	None	N
S/D	0.1981	likely_benign	0.1713	benign	0.461	Stabilizing	0.016	N	0.275	neutral	None	None	None	None	N
S/E	0.2547	likely_benign	0.2297	benign	0.433	Stabilizing	0.016	N	0.277	neutral	None	None	None	None	N
S/F	0.1423	likely_benign	0.1465	benign	-0.774	Destabilizing	0.214	N	0.552	neutral	None	None	None	None	N
S/G	0.0956	likely_benign	0.09	benign	-0.661	Destabilizing	0.012	N	0.281	neutral	N	0.49148228	None	None	N
S/H	0.106	likely_benign	0.096	benign	-1.102	Destabilizing	0.214	N	0.479	neutral	None	None	None	None	N
S/I	0.0791	likely_benign	0.0723	benign	-0.042	Destabilizing	None	N	0.318	neutral	N	0.421987697	None	None	N
S/K	0.203	likely_benign	0.1808	benign	-0.384	Destabilizing	0.016	N	0.275	neutral	None	None	None	None	N
S/L	0.0876	likely_benign	0.0882	benign	-0.042	Destabilizing	0.016	N	0.371	neutral	None	None	None	None	N
S/M	0.1354	likely_benign	0.1358	benign	-0.004	Destabilizing	0.214	N	0.479	neutral	None	None	None	None	N
S/N	0.0668	likely_benign	0.0595	benign	-0.291	Destabilizing	None	N	0.109	neutral	N	0.425910649	None	None	N
S/P	0.7522	likely_pathogenic	0.7234	pathogenic	-0.148	Destabilizing	0.136	N	0.46	neutral	None	None	None	None	N
S/Q	0.1902	likely_benign	0.1706	benign	-0.412	Destabilizing	0.003	N	0.199	neutral	None	None	None	None	N
S/R	0.1641	likely_benign	0.1469	benign	-0.33	Destabilizing	0.055	N	0.446	neutral	N	0.44243754	None	None	N
S/T	0.0589	likely_benign	0.062	benign	-0.372	Destabilizing	None	N	0.11	neutral	N	0.420755546	None	None	N
S/V	0.1004	likely_benign	0.0949	benign	-0.148	Destabilizing	0.016	N	0.371	neutral	None	None	None	None	N
S/W	0.2476	likely_benign	0.2409	benign	-0.763	Destabilizing	0.864	D	0.537	neutral	None	None	None	None	N
S/Y	0.1097	likely_benign	0.106	benign	-0.469	Destabilizing	0.628	D	0.543	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.