TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30141	90646;90647;90648	chr2:178552479;178552478;178552477	chr2:179417206;179417205;179417204
N2AB	28500	85723;85724;85725	chr2:178552479;178552478;178552477	chr2:179417206;179417205;179417204
N2A	27573	82942;82943;82944	chr2:178552479;178552478;178552477	chr2:179417206;179417205;179417204
N2B	21076	63451;63452;63453	chr2:178552479;178552478;178552477	chr2:179417206;179417205;179417204
Novex-1	21201	63826;63827;63828	chr2:178552479;178552478;178552477	chr2:179417206;179417205;179417204
Novex-2	21268	64027;64028;64029	chr2:178552479;178552478;178552477	chr2:179417206;179417205;179417204
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: Ig-148
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3168
• 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
V/I	None	None	None	N	0.103	0.11	0.326074293725	gnomAD-4.0.0	1.37028E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00748E-07	1.16015E-05	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	0.3715	ambiguous	0.3415	ambiguous	-1.42	Destabilizing	0.052	N	0.307	neutral	N	0.498488398	None	None	I
V/C	0.7173	likely_pathogenic	0.684	pathogenic	-1.173	Destabilizing	0.935	D	0.327	neutral	None	None	None	None	I
V/D	0.8042	likely_pathogenic	0.7557	pathogenic	-1.041	Destabilizing	0.484	N	0.459	neutral	D	0.540972525	None	None	I
V/E	0.6594	likely_pathogenic	0.5877	pathogenic	-0.98	Destabilizing	0.555	D	0.388	neutral	None	None	None	None	I
V/F	0.1851	likely_benign	0.1829	benign	-0.905	Destabilizing	0.317	N	0.338	neutral	N	0.478326556	None	None	I
V/G	0.5354	ambiguous	0.4971	ambiguous	-1.798	Destabilizing	0.484	N	0.437	neutral	D	0.529678096	None	None	I
V/H	0.757	likely_pathogenic	0.6901	pathogenic	-1.249	Destabilizing	0.935	D	0.455	neutral	None	None	None	None	I
V/I	0.075	likely_benign	0.0741	benign	-0.467	Destabilizing	None	N	0.103	neutral	N	0.439074735	None	None	I
V/K	0.6475	likely_pathogenic	0.5464	ambiguous	-1.269	Destabilizing	0.555	D	0.399	neutral	None	None	None	None	I
V/L	0.1607	likely_benign	0.1636	benign	-0.467	Destabilizing	None	N	0.082	neutral	N	0.425529434	None	None	I
V/M	0.1453	likely_benign	0.1461	benign	-0.505	Destabilizing	0.38	N	0.366	neutral	None	None	None	None	I
V/N	0.6255	likely_pathogenic	0.5701	pathogenic	-1.215	Destabilizing	0.791	D	0.463	neutral	None	None	None	None	I
V/P	0.9277	likely_pathogenic	0.9318	pathogenic	-0.749	Destabilizing	0.791	D	0.419	neutral	None	None	None	None	I
V/Q	0.6111	likely_pathogenic	0.5219	ambiguous	-1.25	Destabilizing	0.791	D	0.419	neutral	None	None	None	None	I
V/R	0.6081	likely_pathogenic	0.5128	ambiguous	-0.865	Destabilizing	0.555	D	0.465	neutral	None	None	None	None	I
V/S	0.5432	ambiguous	0.5016	ambiguous	-1.824	Destabilizing	0.262	N	0.368	neutral	None	None	None	None	I
V/T	0.4016	ambiguous	0.3571	ambiguous	-1.626	Destabilizing	0.149	N	0.291	neutral	None	None	None	None	I
V/W	0.8286	likely_pathogenic	0.8147	pathogenic	-1.128	Destabilizing	0.935	D	0.499	neutral	None	None	None	None	I
V/Y	0.5355	ambiguous	0.4826	ambiguous	-0.814	Destabilizing	0.555	D	0.337	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.