TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15055	45388;45389;45390	chr2:178621661;178621660;178621659	chr2:179486388;179486387;179486386
N2AB	13414	40465;40466;40467	chr2:178621661;178621660;178621659	chr2:179486388;179486387;179486386
N2A	12487	37684;37685;37686	chr2:178621661;178621660;178621659	chr2:179486388;179486387;179486386
N2B	5990	18193;18194;18195	chr2:178621661;178621660;178621659	chr2:179486388;179486387;179486386
Novex-1	6115	18568;18569;18570	chr2:178621661;178621660;178621659	chr2:179486388;179486387;179486386
Novex-2	6182	18769;18770;18771	chr2:178621661;178621660;178621659	chr2:179486388;179486387;179486386
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-102
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3985
• 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/P	None	None	1.0	D	0.693	0.611	0.633466640759	gnomAD-4.0.0	1.36951E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79989E-06	0	0
S/T	None	None	0.999	D	0.397	0.408	0.505335117028	gnomAD-4.0.0	6.84754E-07	None	None	None	None	N	None	2.99491E-05	0	None	0	0	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	0.2566	likely_benign	0.2283	benign	-0.467	Destabilizing	0.997	D	0.355	neutral	D	0.604560188	None	None	N
S/C	0.5758	likely_pathogenic	0.5637	ambiguous	-0.406	Destabilizing	1.0	D	0.686	prob.neutral	D	0.755048767	None	None	N
S/D	0.7593	likely_pathogenic	0.7805	pathogenic	-0.233	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
S/E	0.9045	likely_pathogenic	0.8937	pathogenic	-0.262	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
S/F	0.8139	likely_pathogenic	0.7649	pathogenic	-0.64	Destabilizing	1.0	D	0.753	deleterious	D	0.671656969	None	None	N
S/G	0.2266	likely_benign	0.2238	benign	-0.697	Destabilizing	0.999	D	0.425	neutral	None	None	None	None	N
S/H	0.8582	likely_pathogenic	0.849	pathogenic	-1.202	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
S/I	0.7345	likely_pathogenic	0.6812	pathogenic	0.027	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
S/K	0.9702	likely_pathogenic	0.9627	pathogenic	-0.843	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
S/L	0.4371	ambiguous	0.383	ambiguous	0.027	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
S/M	0.6733	likely_pathogenic	0.6382	pathogenic	0.198	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
S/N	0.3637	ambiguous	0.387	ambiguous	-0.682	Destabilizing	0.999	D	0.506	neutral	None	None	None	None	N
S/P	0.9284	likely_pathogenic	0.8886	pathogenic	-0.103	Destabilizing	1.0	D	0.693	prob.neutral	D	0.604656531	None	None	N
S/Q	0.8898	likely_pathogenic	0.8828	pathogenic	-0.836	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
S/R	0.9493	likely_pathogenic	0.9354	pathogenic	-0.688	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
S/T	0.1807	likely_benign	0.1777	benign	-0.686	Destabilizing	0.999	D	0.397	neutral	D	0.548472214	None	None	N
S/V	0.7194	likely_pathogenic	0.6822	pathogenic	-0.103	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/W	0.8579	likely_pathogenic	0.8315	pathogenic	-0.662	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
S/Y	0.7284	likely_pathogenic	0.6959	pathogenic	-0.407	Destabilizing	1.0	D	0.755	deleterious	D	0.716135924	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.