TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5930	18013;18014;18015	chr2:178730745;178730744;178730743	chr2:179595472;179595471;179595470
N2AB	5613	17062;17063;17064	chr2:178730745;178730744;178730743	chr2:179595472;179595471;179595470
N2A	4686	14281;14282;14283	chr2:178730745;178730744;178730743	chr2:179595472;179595471;179595470
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-43
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.4823
• 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
S/R	None	None	0.994	D	0.405	0.402	0.439763647824	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	6.33473E-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	0.1111	likely_benign	0.1122	benign	-0.84	Destabilizing	0.148	N	0.197	neutral	None	None	None	None	I
S/C	0.1794	likely_benign	0.1806	benign	-0.616	Destabilizing	0.999	D	0.381	neutral	N	0.491095491	None	None	I
S/D	0.8415	likely_pathogenic	0.8508	pathogenic	-0.376	Destabilizing	0.984	D	0.373	neutral	None	None	None	None	I
S/E	0.9142	likely_pathogenic	0.9237	pathogenic	-0.328	Destabilizing	0.984	D	0.363	neutral	None	None	None	None	I
S/F	0.6974	likely_pathogenic	0.7231	pathogenic	-0.873	Destabilizing	0.999	D	0.386	neutral	None	None	None	None	I
S/G	0.1109	likely_benign	0.1156	benign	-1.139	Destabilizing	0.01	N	0.165	neutral	N	0.415309654	None	None	I
S/H	0.7542	likely_pathogenic	0.7865	pathogenic	-1.532	Destabilizing	1.0	D	0.376	neutral	None	None	None	None	I
S/I	0.4567	ambiguous	0.479	ambiguous	-0.135	Destabilizing	0.994	D	0.386	neutral	N	0.465964973	None	None	I
S/K	0.9487	likely_pathogenic	0.9598	pathogenic	-0.634	Destabilizing	0.984	D	0.381	neutral	None	None	None	None	I
S/L	0.3664	ambiguous	0.3832	ambiguous	-0.135	Destabilizing	0.969	D	0.392	neutral	None	None	None	None	I
S/M	0.4734	ambiguous	0.4884	ambiguous	0.072	Stabilizing	1.0	D	0.377	neutral	None	None	None	None	I
S/N	0.4292	ambiguous	0.4523	ambiguous	-0.749	Destabilizing	0.979	D	0.453	neutral	N	0.495213232	None	None	I
S/P	0.9456	likely_pathogenic	0.9542	pathogenic	-0.336	Destabilizing	0.995	D	0.391	neutral	None	None	None	None	I
S/Q	0.8568	likely_pathogenic	0.8747	pathogenic	-0.821	Destabilizing	0.999	D	0.413	neutral	None	None	None	None	I
S/R	0.903	likely_pathogenic	0.9176	pathogenic	-0.635	Destabilizing	0.994	D	0.405	neutral	D	0.522783835	None	None	I
S/T	0.1619	likely_benign	0.1721	benign	-0.738	Destabilizing	0.959	D	0.387	neutral	N	0.468045273	None	None	I
S/V	0.4111	ambiguous	0.4305	ambiguous	-0.336	Destabilizing	0.969	D	0.401	neutral	None	None	None	None	I
S/W	0.8543	likely_pathogenic	0.8677	pathogenic	-0.854	Destabilizing	1.0	D	0.506	neutral	None	None	None	None	I
S/Y	0.6134	likely_pathogenic	0.6328	pathogenic	-0.567	Destabilizing	0.999	D	0.391	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.