TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4837	14734;14735;14736	chr2:178735937;178735936;178735935	chr2:179600664;179600663;179600662
N2AB	4520	13783;13784;13785	chr2:178735937;178735936;178735935	chr2:179600664;179600663;179600662
N2A	3593	11002;11003;11004	chr2:178735937;178735936;178735935	chr2:179600664;179600663;179600662
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-31
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.7185
• 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
P/H	rs1291141509	0.125	0.928	N	0.346	0.335	0.564429724435	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
P/H	rs1291141509	0.125	0.928	N	0.346	0.335	0.564429724435	gnomAD-4.0.0	1.36837E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79889E-06	0	0
P/L	None	None	0.001	N	0.254	0.288	0.558499945537	gnomAD-4.0.0	3.42094E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49724E-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
P/A	0.0711	likely_benign	0.0641	benign	-0.326	Destabilizing	0.09	N	0.294	neutral	N	0.482006266	None	None	I
P/C	0.3841	ambiguous	0.3115	benign	-0.786	Destabilizing	0.944	D	0.363	neutral	None	None	None	None	I
P/D	0.3236	likely_benign	0.2503	benign	-0.165	Destabilizing	0.002	N	0.193	neutral	None	None	None	None	I
P/E	0.2254	likely_benign	0.1821	benign	-0.262	Destabilizing	0.241	N	0.267	neutral	None	None	None	None	I
P/F	0.3131	likely_benign	0.2494	benign	-0.606	Destabilizing	0.69	D	0.371	neutral	None	None	None	None	I
P/G	0.2368	likely_benign	0.1929	benign	-0.406	Destabilizing	0.116	N	0.305	neutral	None	None	None	None	I
P/H	0.1453	likely_benign	0.1174	benign	0.06	Stabilizing	0.928	D	0.346	neutral	N	0.508801056	None	None	I
P/I	0.2043	likely_benign	0.1754	benign	-0.251	Destabilizing	0.241	N	0.399	neutral	None	None	None	None	I
P/K	0.2094	likely_benign	0.1738	benign	-0.348	Destabilizing	0.241	N	0.275	neutral	None	None	None	None	I
P/L	0.0965	likely_benign	0.084	benign	-0.251	Destabilizing	0.001	N	0.254	neutral	N	0.49645134	None	None	I
P/M	0.2559	likely_benign	0.2169	benign	-0.585	Destabilizing	0.69	D	0.343	neutral	None	None	None	None	I
P/N	0.2284	likely_benign	0.1806	benign	-0.185	Destabilizing	0.241	N	0.385	neutral	None	None	None	None	I
P/Q	0.1308	likely_benign	0.1101	benign	-0.348	Destabilizing	0.69	D	0.315	neutral	None	None	None	None	I
P/R	0.1406	likely_benign	0.1167	benign	0.052	Stabilizing	0.627	D	0.381	neutral	N	0.487029605	None	None	I
P/S	0.0924	likely_benign	0.0792	benign	-0.528	Destabilizing	0.001	N	0.152	neutral	N	0.426534581	None	None	I
P/T	0.0858	likely_benign	0.0737	benign	-0.527	Destabilizing	0.193	N	0.269	neutral	N	0.484932479	None	None	I
P/V	0.1495	likely_benign	0.1289	benign	-0.248	Destabilizing	0.241	N	0.337	neutral	None	None	None	None	I
P/W	0.4943	ambiguous	0.4062	ambiguous	-0.673	Destabilizing	0.981	D	0.451	neutral	None	None	None	None	I
P/Y	0.2936	likely_benign	0.2407	benign	-0.401	Destabilizing	0.818	D	0.364	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.