TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7689	23290;23291;23292	chr2:178720954;178720953;178720952	chr2:179585681;179585680;179585679
N2AB	7372	22339;22340;22341	chr2:178720954;178720953;178720952	chr2:179585681;179585680;179585679
N2A	6445	19558;19559;19560	chr2:178720954;178720953;178720952	chr2:179585681;179585680;179585679
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-61
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.589
• 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
D/N	rs727505052	-0.141	0.101	N	0.278	0.068	0.144782658237	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	8.28E-05	0	None	0	1.02606E-04	None	0	None	0	0	0
D/N	rs727505052	-0.141	0.101	N	0.278	0.068	0.144782658237	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	7.24E-05	1.30941E-04	0	0	0	None	0	0	0	0	4.77555E-04
D/N	rs727505052	-0.141	0.101	N	0.278	0.068	0.144782658237	gnomAD-4.0.0	1.93654E-05	None	None	None	None	N	None	8.0156E-05	3.34717E-05	None	0	1.12329E-04	None	0	0	1.71034E-06	0	2.5859E-04

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
D/A	0.1007	likely_benign	0.131	benign	-0.189	Destabilizing	0.047	N	0.365	neutral	N	0.405823379	None	None	N
D/C	0.4016	ambiguous	0.584	pathogenic	0.18	Stabilizing	0.002	N	0.377	neutral	None	None	None	None	N
D/E	0.1066	likely_benign	0.1391	benign	-0.306	Destabilizing	0.002	N	0.121	neutral	N	0.346292286	None	None	N
D/F	0.2571	likely_benign	0.3722	ambiguous	-0.289	Destabilizing	0.716	D	0.544	neutral	None	None	None	None	N
D/G	0.1237	likely_benign	0.1763	benign	-0.366	Destabilizing	0.183	N	0.405	neutral	N	0.465853117	None	None	N
D/H	0.093	likely_benign	0.1553	benign	-0.185	Destabilizing	0.002	N	0.255	neutral	N	0.458388427	None	None	N
D/I	0.1688	likely_benign	0.2391	benign	0.218	Stabilizing	0.418	N	0.576	neutral	None	None	None	None	N
D/K	0.1422	likely_benign	0.2404	benign	0.414	Stabilizing	0.129	N	0.421	neutral	None	None	None	None	N
D/L	0.1723	likely_benign	0.2621	benign	0.218	Stabilizing	0.129	N	0.528	neutral	None	None	None	None	N
D/M	0.3165	likely_benign	0.4269	ambiguous	0.381	Stabilizing	0.94	D	0.526	neutral	None	None	None	None	N
D/N	0.0657	likely_benign	0.0854	benign	0.222	Stabilizing	0.101	N	0.278	neutral	N	0.424025137	None	None	N
D/P	0.6029	likely_pathogenic	0.8039	pathogenic	0.104	Stabilizing	0.593	D	0.474	neutral	None	None	None	None	N
D/Q	0.128	likely_benign	0.2157	benign	0.223	Stabilizing	0.264	N	0.3	neutral	None	None	None	None	N
D/R	0.1363	likely_benign	0.2576	benign	0.493	Stabilizing	0.418	N	0.531	neutral	None	None	None	None	N
D/S	0.0744	likely_benign	0.0931	benign	0.11	Stabilizing	0.012	N	0.133	neutral	None	None	None	None	N
D/T	0.1076	likely_benign	0.1594	benign	0.242	Stabilizing	0.004	N	0.194	neutral	None	None	None	None	N
D/V	0.1097	likely_benign	0.1425	benign	0.104	Stabilizing	0.101	N	0.524	neutral	N	0.429759031	None	None	N
D/W	0.6153	likely_pathogenic	0.7614	pathogenic	-0.212	Destabilizing	0.983	D	0.516	neutral	None	None	None	None	N
D/Y	0.0992	likely_benign	0.1384	benign	-0.058	Destabilizing	0.487	N	0.549	neutral	N	0.462332809	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.