TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21714	65365;65366;65367	chr2:178584411;178584410;178584409	chr2:179449138;179449137;179449136
N2AB	20073	60442;60443;60444	chr2:178584411;178584410;178584409	chr2:179449138;179449137;179449136
N2A	19146	57661;57662;57663	chr2:178584411;178584410;178584409	chr2:179449138;179449137;179449136
N2B	12649	38170;38171;38172	chr2:178584411;178584410;178584409	chr2:179449138;179449137;179449136
Novex-1	12774	38545;38546;38547	chr2:178584411;178584410;178584409	chr2:179449138;179449137;179449136
Novex-2	12841	38746;38747;38748	chr2:178584411;178584410;178584409	chr2:179449138;179449137;179449136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-45
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1597
• 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
V/G	rs751864769	-2.318	1.0	N	0.817	0.45	0.871969193956	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	1.65948E-04
V/G	rs751864769	-2.318	1.0	N	0.817	0.45	0.871969193956	gnomAD-4.0.0	1.59221E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	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
V/A	0.6927	likely_pathogenic	0.6313	pathogenic	-1.207	Destabilizing	0.999	D	0.559	neutral	D	0.523751336	None	None	N
V/C	0.8627	likely_pathogenic	0.825	pathogenic	-0.508	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/D	0.9777	likely_pathogenic	0.9744	pathogenic	-1.533	Destabilizing	1.0	D	0.863	deleterious	N	0.479607537	None	None	N
V/E	0.936	likely_pathogenic	0.928	pathogenic	-1.274	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/F	0.7714	likely_pathogenic	0.7335	pathogenic	-0.597	Destabilizing	1.0	D	0.814	deleterious	N	0.487257767	None	None	N
V/G	0.7875	likely_pathogenic	0.7622	pathogenic	-1.763	Destabilizing	1.0	D	0.817	deleterious	N	0.50372278	None	None	N
V/H	0.9736	likely_pathogenic	0.9665	pathogenic	-1.77	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.134	likely_benign	0.1217	benign	0.346	Stabilizing	0.997	D	0.493	neutral	N	0.471266432	None	None	N
V/K	0.9566	likely_pathogenic	0.9536	pathogenic	-0.663	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/L	0.5342	ambiguous	0.4714	ambiguous	0.346	Stabilizing	0.997	D	0.546	neutral	N	0.47317921	None	None	N
V/M	0.6389	likely_pathogenic	0.5807	pathogenic	0.233	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
V/N	0.926	likely_pathogenic	0.9094	pathogenic	-1.077	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/P	0.928	likely_pathogenic	0.9073	pathogenic	-0.144	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/Q	0.8969	likely_pathogenic	0.8805	pathogenic	-0.788	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/R	0.9252	likely_pathogenic	0.918	pathogenic	-0.902	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/S	0.7966	likely_pathogenic	0.7605	pathogenic	-1.676	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/T	0.7483	likely_pathogenic	0.6715	pathogenic	-1.258	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
V/W	0.9915	likely_pathogenic	0.9888	pathogenic	-1.173	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Y	0.9623	likely_pathogenic	0.9546	pathogenic	-0.642	Destabilizing	1.0	D	0.817	deleterious	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.