TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3267	10024;10025;10026	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441
N2AB	3267	10024;10025;10026	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441
N2A	3267	10024;10025;10026	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441
N2B	3221	9886;9887;9888	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441
Novex-1	3221	9886;9887;9888	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441
Novex-2	3221	9886;9887;9888	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441
Novex-3	3267	10024;10025;10026	chr2:178764716;178764715;178764714	chr2:179629443;179629442;179629441

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-23
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7815
• Predicted PPI site: I

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
Q/K	None	None	0.454	N	0.38	0.303	0.224531998449	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
Q/A	0.1878	likely_benign	0.2511	benign	-0.171	Destabilizing	0.016	N	0.215	neutral	None	None	None	None	I
Q/C	0.7731	likely_pathogenic	0.9046	pathogenic	0.103	Stabilizing	0.993	D	0.481	neutral	None	None	None	None	I
Q/D	0.4961	ambiguous	0.6773	pathogenic	0.037	Stabilizing	0.016	N	0.179	neutral	None	None	None	None	I
Q/E	0.0941	likely_benign	0.1285	benign	0.021	Stabilizing	0.454	N	0.373	neutral	N	0.499873248	None	None	I
Q/F	0.7004	likely_pathogenic	0.8356	pathogenic	-0.346	Destabilizing	0.974	D	0.483	neutral	None	None	None	None	I
Q/G	0.4778	ambiguous	0.6637	pathogenic	-0.367	Destabilizing	0.728	D	0.453	neutral	None	None	None	None	I
Q/H	0.3021	likely_benign	0.4433	ambiguous	-0.177	Destabilizing	0.989	D	0.425	neutral	D	0.541911499	None	None	I
Q/I	0.3239	likely_benign	0.4657	ambiguous	0.262	Stabilizing	0.949	D	0.489	neutral	None	None	None	None	I
Q/K	0.105	likely_benign	0.1845	benign	-0.003	Destabilizing	0.454	N	0.38	neutral	N	0.470615133	None	None	I
Q/L	0.1266	likely_benign	0.1937	benign	0.262	Stabilizing	0.801	D	0.454	neutral	N	0.510611983	None	None	I
Q/M	0.3464	ambiguous	0.4372	ambiguous	0.324	Stabilizing	0.991	D	0.42	neutral	None	None	None	None	I
Q/N	0.3768	ambiguous	0.4972	ambiguous	-0.321	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	I
Q/P	0.1353	likely_benign	0.2062	benign	0.146	Stabilizing	0.966	D	0.433	neutral	N	0.473998295	None	None	I
Q/R	0.1392	likely_benign	0.2272	benign	0.161	Stabilizing	0.051	N	0.253	neutral	N	0.499980229	None	None	I
Q/S	0.2626	likely_benign	0.342	ambiguous	-0.308	Destabilizing	0.525	D	0.343	neutral	None	None	None	None	I
Q/T	0.2226	likely_benign	0.3086	benign	-0.17	Destabilizing	0.842	D	0.411	neutral	None	None	None	None	I
Q/V	0.2148	likely_benign	0.3019	benign	0.146	Stabilizing	0.728	D	0.475	neutral	None	None	None	None	I
Q/W	0.6833	likely_pathogenic	0.8778	pathogenic	-0.362	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	I
Q/Y	0.5421	ambiguous	0.7283	pathogenic	-0.097	Destabilizing	0.991	D	0.443	neutral	None	None	None	None	I

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.