TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8306	25141;25142;25143	chr2:178718090;178718089;178718088	chr2:179582817;179582816;179582815
N2AB	7989	24190;24191;24192	chr2:178718090;178718089;178718088	chr2:179582817;179582816;179582815
N2A	7062	21409;21410;21411	chr2:178718090;178718089;178718088	chr2:179582817;179582816;179582815
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-68
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.5712
• 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
S/L	rs776712129	0.228	0.932	D	0.428	0.48	0.71767939224	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
S/L	rs776712129	0.228	0.932	D	0.428	0.48	0.71767939224	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
S/L	rs776712129	0.228	0.932	D	0.428	0.48	0.71767939224	gnomAD-4.0.0	1.36365E-05	None	None	None	None	N	None	0	0	None	0	2.22826E-05	None	0	0	1.78009E-05	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
S/A	0.0826	likely_benign	0.0852	benign	-0.115	Destabilizing	0.004	N	0.146	neutral	N	0.482209436	None	None	N
S/C	0.2703	likely_benign	0.2963	benign	-0.259	Destabilizing	0.997	D	0.496	neutral	None	None	None	None	N
S/D	0.614	likely_pathogenic	0.7057	pathogenic	-0.01	Destabilizing	0.907	D	0.408	neutral	None	None	None	None	N
S/E	0.7199	likely_pathogenic	0.7663	pathogenic	-0.107	Destabilizing	0.932	D	0.399	neutral	None	None	None	None	N
S/F	0.317	likely_benign	0.3834	ambiguous	-0.733	Destabilizing	0.997	D	0.522	neutral	None	None	None	None	N
S/G	0.1275	likely_benign	0.1669	benign	-0.208	Destabilizing	0.027	N	0.126	neutral	None	None	None	None	N
S/H	0.5562	ambiguous	0.6518	pathogenic	-0.63	Destabilizing	0.999	D	0.488	neutral	None	None	None	None	N
S/I	0.252	likely_benign	0.3136	benign	-0.004	Destabilizing	0.992	D	0.517	neutral	None	None	None	None	N
S/K	0.8611	likely_pathogenic	0.9136	pathogenic	-0.493	Destabilizing	0.973	D	0.405	neutral	None	None	None	None	N
S/L	0.1327	likely_benign	0.1531	benign	-0.004	Destabilizing	0.932	D	0.428	neutral	D	0.530560744	None	None	N
S/M	0.2685	likely_benign	0.3059	benign	-0.016	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
S/N	0.1977	likely_benign	0.2541	benign	-0.147	Destabilizing	0.534	D	0.446	neutral	None	None	None	None	N
S/P	0.1285	likely_benign	0.1387	benign	-0.013	Destabilizing	0.011	N	0.225	neutral	N	0.469280211	None	None	N
S/Q	0.6523	likely_pathogenic	0.7205	pathogenic	-0.369	Destabilizing	0.997	D	0.47	neutral	None	None	None	None	N
S/R	0.8199	likely_pathogenic	0.8857	pathogenic	-0.259	Destabilizing	0.992	D	0.466	neutral	None	None	None	None	N
S/T	0.1126	likely_benign	0.13	benign	-0.216	Destabilizing	0.299	N	0.407	neutral	N	0.48803933	None	None	N
S/V	0.2278	likely_benign	0.2723	benign	-0.013	Destabilizing	0.871	D	0.433	neutral	None	None	None	None	N
S/W	0.4759	ambiguous	0.5624	ambiguous	-0.826	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
S/Y	0.2921	likely_benign	0.3531	ambiguous	-0.518	Destabilizing	0.997	D	0.519	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.