TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7460	22603;22604;22605	chr2:178722409;178722408;178722407	chr2:179587136;179587135;179587134
N2AB	7143	21652;21653;21654	chr2:178722409;178722408;178722407	chr2:179587136;179587135;179587134
N2A	6216	18871;18872;18873	chr2:178722409;178722408;178722407	chr2:179587136;179587135;179587134
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-59
• Domain position: 42
• Structural Position: 69
• Q(SASA): 0.4695
• 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
R/I	None	None	0.863	N	0.37	0.261	0.612832922585	gnomAD-4.0.0	1.59202E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-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
R/A	0.2322	likely_benign	0.2144	benign	0.133	Stabilizing	0.329	N	0.32	neutral	None	None	None	None	N
R/C	0.2381	likely_benign	0.2049	benign	-0.161	Destabilizing	0.995	D	0.342	neutral	None	None	None	None	N
R/D	0.4333	ambiguous	0.3955	ambiguous	-0.294	Destabilizing	0.704	D	0.376	neutral	None	None	None	None	N
R/E	0.2091	likely_benign	0.1935	benign	-0.246	Destabilizing	0.329	N	0.295	neutral	None	None	None	None	N
R/F	0.4588	ambiguous	0.4179	ambiguous	-0.172	Destabilizing	0.944	D	0.357	neutral	None	None	None	None	N
R/G	0.1519	likely_benign	0.1463	benign	-0.015	Destabilizing	0.27	N	0.361	neutral	N	0.481342645	None	None	N
R/H	0.09	likely_benign	0.0886	benign	-0.582	Destabilizing	0.981	D	0.323	neutral	None	None	None	None	N
R/I	0.2283	likely_benign	0.216	benign	0.48	Stabilizing	0.863	D	0.37	neutral	N	0.483940233	None	None	N
R/K	0.0845	likely_benign	0.0844	benign	-0.065	Destabilizing	0.002	N	0.183	neutral	N	0.403225791	None	None	N
R/L	0.1796	likely_benign	0.1637	benign	0.48	Stabilizing	0.329	N	0.362	neutral	None	None	None	None	N
R/M	0.2086	likely_benign	0.196	benign	-0.035	Destabilizing	0.981	D	0.339	neutral	None	None	None	None	N
R/N	0.3563	ambiguous	0.3302	benign	0.002	Stabilizing	0.704	D	0.262	neutral	None	None	None	None	N
R/P	0.3186	likely_benign	0.2954	benign	0.383	Stabilizing	0.828	D	0.365	neutral	None	None	None	None	N
R/Q	0.0854	likely_benign	0.0846	benign	-0.011	Destabilizing	0.704	D	0.321	neutral	None	None	None	None	N
R/S	0.2612	likely_benign	0.2502	benign	-0.136	Destabilizing	0.023	N	0.207	neutral	N	0.450518305	None	None	N
R/T	0.1317	likely_benign	0.1284	benign	0.022	Stabilizing	0.01	N	0.179	neutral	N	0.418715318	None	None	N
R/V	0.2671	likely_benign	0.2522	benign	0.383	Stabilizing	0.543	D	0.388	neutral	None	None	None	None	N
R/W	0.1473	likely_benign	0.1338	benign	-0.377	Destabilizing	0.995	D	0.361	neutral	None	None	None	None	N
R/Y	0.3161	likely_benign	0.2834	benign	0.039	Stabilizing	0.981	D	0.358	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.