TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8714	26365;26366;26367	chr2:178715046;178715045;178715044	chr2:179579773;179579772;179579771
N2AB	8397	25414;25415;25416	chr2:178715046;178715045;178715044	chr2:179579773;179579772;179579771
N2A	7470	22633;22634;22635	chr2:178715046;178715045;178715044	chr2:179579773;179579772;179579771
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-72
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1695
• 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
Q/E	None	None	None	N	0.226	0.158	0.119812018005	gnomAD-4.0.0	1.59179E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85923E-06	0	0
Q/H	rs2077266939	None	None	N	0.275	0.146	0.0884992946249	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	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	0.2299	likely_benign	0.2715	benign	-0.828	Destabilizing	0.148	N	0.488	neutral	None	None	None	None	N
Q/C	0.3776	ambiguous	0.4667	ambiguous	-0.147	Destabilizing	0.912	D	0.637	neutral	None	None	None	None	N
Q/D	0.413	ambiguous	0.5286	ambiguous	-0.816	Destabilizing	0.025	N	0.449	neutral	None	None	None	None	N
Q/E	0.0911	likely_benign	0.1049	benign	-0.651	Destabilizing	None	N	0.226	neutral	N	0.425346849	None	None	N
Q/F	0.3916	ambiguous	0.4307	ambiguous	-0.329	Destabilizing	0.451	N	0.609	neutral	None	None	None	None	N
Q/G	0.2909	likely_benign	0.3779	ambiguous	-1.243	Destabilizing	0.148	N	0.559	neutral	None	None	None	None	N
Q/H	0.1004	likely_benign	0.1166	benign	-0.946	Destabilizing	None	N	0.275	neutral	N	0.479007976	None	None	N
Q/I	0.2327	likely_benign	0.2559	benign	0.264	Stabilizing	0.37	N	0.62	neutral	None	None	None	None	N
Q/K	0.1108	likely_benign	0.1422	benign	-0.377	Destabilizing	0.05	N	0.461	neutral	N	0.484528439	None	None	N
Q/L	0.1018	likely_benign	0.1188	benign	0.264	Stabilizing	0.112	N	0.583	neutral	N	0.501671405	None	None	N
Q/M	0.3052	likely_benign	0.3173	benign	0.69	Stabilizing	0.784	D	0.505	neutral	None	None	None	None	N
Q/N	0.2496	likely_benign	0.2922	benign	-1.038	Destabilizing	0.059	N	0.478	neutral	None	None	None	None	N
Q/P	0.6269	likely_pathogenic	0.7603	pathogenic	-0.069	Destabilizing	0.162	N	0.531	neutral	N	0.49148255	None	None	N
Q/R	0.0921	likely_benign	0.1158	benign	-0.398	Destabilizing	0.076	N	0.491	neutral	N	0.473503369	None	None	N
Q/S	0.2271	likely_benign	0.2471	benign	-1.229	Destabilizing	0.08	N	0.438	neutral	None	None	None	None	N
Q/T	0.1651	likely_benign	0.1811	benign	-0.854	Destabilizing	None	N	0.349	neutral	None	None	None	None	N
Q/V	0.1745	likely_benign	0.1898	benign	-0.069	Destabilizing	0.048	N	0.575	neutral	None	None	None	None	N
Q/W	0.2825	likely_benign	0.3751	ambiguous	-0.196	Destabilizing	0.981	D	0.611	neutral	None	None	None	None	N
Q/Y	0.2103	likely_benign	0.2485	benign	0.048	Stabilizing	0.105	N	0.561	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.