TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27319	82180;82181;82182	chr2:178564177;178564176;178564175	chr2:179428904;179428903;179428902
N2AB	25678	77257;77258;77259	chr2:178564177;178564176;178564175	chr2:179428904;179428903;179428902
N2A	24751	74476;74477;74478	chr2:178564177;178564176;178564175	chr2:179428904;179428903;179428902
N2B	18254	54985;54986;54987	chr2:178564177;178564176;178564175	chr2:179428904;179428903;179428902
Novex-1	18379	55360;55361;55362	chr2:178564177;178564176;178564175	chr2:179428904;179428903;179428902
Novex-2	18446	55561;55562;55563	chr2:178564177;178564176;178564175	chr2:179428904;179428903;179428902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-140
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.1742
• 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
T/I	rs1175606376	0.101	0.193	N	0.351	0.159	0.244539031024	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	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
T/A	0.068	likely_benign	0.072	benign	-0.14	Destabilizing	None	N	0.166	neutral	N	0.401624628	None	None	N
T/C	0.3551	ambiguous	0.3752	ambiguous	-0.302	Destabilizing	0.944	D	0.375	neutral	None	None	None	None	N
T/D	0.2256	likely_benign	0.2383	benign	-0.118	Destabilizing	0.818	D	0.345	neutral	None	None	None	None	N
T/E	0.1905	likely_benign	0.201	benign	-0.216	Destabilizing	0.388	N	0.363	neutral	None	None	None	None	N
T/F	0.1837	likely_benign	0.2017	benign	-0.802	Destabilizing	0.69	D	0.406	neutral	None	None	None	None	N
T/G	0.1508	likely_benign	0.1623	benign	-0.19	Destabilizing	0.241	N	0.381	neutral	None	None	None	None	N
T/H	0.1832	likely_benign	0.1937	benign	-0.375	Destabilizing	0.981	D	0.403	neutral	None	None	None	None	N
T/I	0.1344	likely_benign	0.1518	benign	-0.128	Destabilizing	0.193	N	0.351	neutral	N	0.478354615	None	None	N
T/K	0.1356	likely_benign	0.1478	benign	-0.3	Destabilizing	0.324	N	0.367	neutral	N	0.405857011	None	None	N
T/L	0.0927	likely_benign	0.1005	benign	-0.128	Destabilizing	0.002	N	0.237	neutral	None	None	None	None	N
T/M	0.0793	likely_benign	0.0813	benign	-0.113	Destabilizing	0.69	D	0.377	neutral	None	None	None	None	N
T/N	0.0815	likely_benign	0.0854	benign	-0.036	Destabilizing	0.818	D	0.414	neutral	None	None	None	None	N
T/P	0.0933	likely_benign	0.1022	benign	-0.109	Destabilizing	0.773	D	0.353	neutral	N	0.466790827	None	None	N
T/Q	0.1732	likely_benign	0.1818	benign	-0.273	Destabilizing	0.818	D	0.375	neutral	None	None	None	None	N
T/R	0.1247	likely_benign	0.1389	benign	-0.007	Destabilizing	0.627	D	0.355	neutral	N	0.415708646	None	None	N
T/S	0.0903	likely_benign	0.0941	benign	-0.184	Destabilizing	0.09	N	0.455	neutral	N	0.418916735	None	None	N
T/V	0.1107	likely_benign	0.1197	benign	-0.109	Destabilizing	0.116	N	0.419	neutral	None	None	None	None	N
T/W	0.4604	ambiguous	0.4993	ambiguous	-0.892	Destabilizing	0.981	D	0.455	neutral	None	None	None	None	N
T/Y	0.2162	likely_benign	0.245	benign	-0.574	Destabilizing	0.932	D	0.409	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.