TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6647	20164;20165;20166	chr2:178727639;178727638;178727637	chr2:179592366;179592365;179592364
N2AB	6330	19213;19214;19215	chr2:178727639;178727638;178727637	chr2:179592366;179592365;179592364
N2A	5403	16432;16433;16434	chr2:178727639;178727638;178727637	chr2:179592366;179592365;179592364
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-50
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3911
• 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
H/Q	rs565190478	-0.723	None	N	0.174	0.097	0.0401082797425	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/Q	rs565190478	-0.723	None	N	0.174	0.097	0.0401082797425	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
H/Q	rs565190478	-0.723	None	N	0.174	0.097	0.0401082797425	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	0	0
H/R	rs757799209	-1.138	None	N	0.194	0.154	0.197625483188	gnomAD-2.1.1	4.19E-06	None	None	None	None	N	None	0	0	None	0	5.66E-05	None	0	None	0	0	0
H/R	rs757799209	-1.138	None	N	0.194	0.154	0.197625483188	gnomAD-4.0.0	2.75954E-06	None	None	None	None	N	None	0	0	None	0	2.52755E-05	None	0	0	2.71139E-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
H/A	0.1429	likely_benign	0.1571	benign	-1.331	Destabilizing	0.007	N	0.425	neutral	None	None	None	None	N
H/C	0.1235	likely_benign	0.1311	benign	-0.552	Destabilizing	0.864	D	0.561	neutral	None	None	None	None	N
H/D	0.1352	likely_benign	0.139	benign	-0.888	Destabilizing	0.024	N	0.398	neutral	N	0.498752183	None	None	N
H/E	0.0943	likely_benign	0.1019	benign	-0.739	Destabilizing	0.007	N	0.321	neutral	None	None	None	None	N
H/F	0.2089	likely_benign	0.2099	benign	0.182	Stabilizing	0.628	D	0.557	neutral	None	None	None	None	N
H/G	0.2192	likely_benign	0.255	benign	-1.725	Destabilizing	0.031	N	0.451	neutral	None	None	None	None	N
H/I	0.1392	likely_benign	0.1336	benign	-0.206	Destabilizing	0.136	N	0.593	neutral	None	None	None	None	N
H/K	0.1026	likely_benign	0.1181	benign	-0.846	Destabilizing	0.007	N	0.301	neutral	None	None	None	None	N
H/L	0.0711	likely_benign	0.069	benign	-0.206	Destabilizing	0.024	N	0.461	neutral	N	0.392798153	None	None	N
H/M	0.219	likely_benign	0.2272	benign	-0.403	Destabilizing	0.356	N	0.574	neutral	None	None	None	None	N
H/N	0.08	likely_benign	0.0792	benign	-1.147	Destabilizing	0.024	N	0.407	neutral	N	0.458174996	None	None	N
H/P	0.5679	likely_pathogenic	0.6326	pathogenic	-0.565	Destabilizing	0.106	N	0.569	neutral	N	0.518031377	None	None	N
H/Q	0.0669	likely_benign	0.0715	benign	-0.828	Destabilizing	None	N	0.174	neutral	N	0.368361069	None	None	N
H/R	0.0664	likely_benign	0.0815	benign	-1.087	Destabilizing	None	N	0.194	neutral	N	0.419059248	None	None	N
H/S	0.1206	likely_benign	0.1355	benign	-1.328	Destabilizing	0.016	N	0.389	neutral	None	None	None	None	N
H/T	0.1086	likely_benign	0.1154	benign	-1.071	Destabilizing	0.031	N	0.465	neutral	None	None	None	None	N
H/V	0.1155	likely_benign	0.1158	benign	-0.565	Destabilizing	0.072	N	0.541	neutral	None	None	None	None	N
H/W	0.2463	likely_benign	0.2689	benign	0.636	Stabilizing	0.864	D	0.56	neutral	None	None	None	None	N
H/Y	0.0803	likely_benign	0.0794	benign	0.628	Stabilizing	0.106	N	0.494	neutral	N	0.456078841	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.