TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7060	21403;21404;21405	chr2:178724081;178724080;178724079	chr2:179588808;179588807;179588806
N2AB	6743	20452;20453;20454	chr2:178724081;178724080;178724079	chr2:179588808;179588807;179588806
N2A	5816	17671;17672;17673	chr2:178724081;178724080;178724079	chr2:179588808;179588807;179588806
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-55
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.47
• 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/F	rs751613786	-0.979	0.061	N	0.239	0.261	0.555277862696	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
S/F	rs751613786	-0.979	0.061	N	0.239	0.261	0.555277862696	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/F	rs751613786	-0.979	0.061	N	0.239	0.261	0.555277862696	gnomAD-4.0.0	6.57168E-06	None	None	None	None	N	None	2.41185E-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	0.0822	likely_benign	0.0811	benign	-0.426	Destabilizing	0.977	D	0.412	neutral	N	0.454428348	None	None	N
S/C	0.2029	likely_benign	0.2016	benign	-0.231	Destabilizing	1.0	D	0.483	neutral	N	0.510591218	None	None	N
S/D	0.3456	ambiguous	0.3212	benign	0.021	Stabilizing	0.998	D	0.393	neutral	None	None	None	None	N
S/E	0.4835	ambiguous	0.4648	ambiguous	-0.07	Destabilizing	0.998	D	0.392	neutral	None	None	None	None	N
S/F	0.1985	likely_benign	0.1827	benign	-0.986	Destabilizing	0.061	N	0.239	neutral	N	0.477256317	None	None	N
S/G	0.0964	likely_benign	0.1011	benign	-0.549	Destabilizing	0.998	D	0.378	neutral	None	None	None	None	N
S/H	0.339	likely_benign	0.327	benign	-1.048	Destabilizing	0.999	D	0.498	neutral	None	None	None	None	N
S/I	0.2159	likely_benign	0.2064	benign	-0.228	Destabilizing	0.985	D	0.456	neutral	None	None	None	None	N
S/K	0.5496	ambiguous	0.5499	ambiguous	-0.49	Destabilizing	0.998	D	0.401	neutral	None	None	None	None	N
S/L	0.1264	likely_benign	0.1208	benign	-0.228	Destabilizing	0.971	D	0.459	neutral	None	None	None	None	N
S/M	0.2881	likely_benign	0.2751	benign	0.126	Stabilizing	0.999	D	0.499	neutral	None	None	None	None	N
S/N	0.1438	likely_benign	0.139	benign	-0.201	Destabilizing	0.998	D	0.416	neutral	None	None	None	None	N
S/P	0.1118	likely_benign	0.1071	benign	-0.265	Destabilizing	0.999	D	0.479	neutral	N	0.494246787	None	None	N
S/Q	0.4497	ambiguous	0.4427	ambiguous	-0.491	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
S/R	0.4326	ambiguous	0.4404	ambiguous	-0.236	Destabilizing	0.999	D	0.474	neutral	None	None	None	None	N
S/T	0.0944	likely_benign	0.0918	benign	-0.317	Destabilizing	0.997	D	0.389	neutral	N	0.484509796	None	None	N
S/V	0.2093	likely_benign	0.1974	benign	-0.265	Destabilizing	0.985	D	0.461	neutral	None	None	None	None	N
S/W	0.3545	ambiguous	0.3461	ambiguous	-0.968	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	N
S/Y	0.2015	likely_benign	0.1899	benign	-0.699	Destabilizing	0.961	D	0.435	neutral	N	0.503754363	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.