TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7453	22582;22583;22584	chr2:178722430;178722429;178722428	chr2:179587157;179587156;179587155
N2AB	7136	21631;21632;21633	chr2:178722430;178722429;178722428	chr2:179587157;179587156;179587155
N2A	6209	18850;18851;18852	chr2:178722430;178722429;178722428	chr2:179587157;179587156;179587155
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-59
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.3006
• 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
Y/C	rs753063571	None	0.998	D	0.536	0.715	0.852661866299	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-06	0	0
Y/N	None	None	0.886	N	0.567	0.534	0.791150215051	gnomAD-4.0.0	1.23181E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52937E-05	0	1.65717E-05

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
Y/A	0.6849	likely_pathogenic	0.6108	pathogenic	-2.167	Highly Destabilizing	0.681	D	0.487	neutral	None	None	None	None	N
Y/C	0.339	likely_benign	0.2888	benign	-0.876	Destabilizing	0.998	D	0.536	neutral	D	0.547212749	None	None	N
Y/D	0.5722	likely_pathogenic	0.4865	ambiguous	-0.271	Destabilizing	0.886	D	0.57	neutral	D	0.528855004	None	None	N
Y/E	0.6704	likely_pathogenic	0.5839	pathogenic	-0.179	Destabilizing	0.912	D	0.519	neutral	None	None	None	None	N
Y/F	0.0876	likely_benign	0.0866	benign	-0.91	Destabilizing	0.003	N	0.212	neutral	N	0.441368465	None	None	N
Y/G	0.6086	likely_pathogenic	0.5421	ambiguous	-2.478	Highly Destabilizing	0.912	D	0.519	neutral	None	None	None	None	N
Y/H	0.1743	likely_benign	0.1579	benign	-0.808	Destabilizing	0.017	N	0.308	neutral	N	0.508851419	None	None	N
Y/I	0.6317	likely_pathogenic	0.5661	pathogenic	-1.234	Destabilizing	0.076	N	0.457	neutral	None	None	None	None	N
Y/K	0.6092	likely_pathogenic	0.5178	ambiguous	-0.826	Destabilizing	0.556	D	0.523	neutral	None	None	None	None	N
Y/L	0.5203	ambiguous	0.4516	ambiguous	-1.234	Destabilizing	0.001	N	0.29	neutral	None	None	None	None	N
Y/M	0.6163	likely_pathogenic	0.5516	ambiguous	-0.917	Destabilizing	0.219	N	0.347	neutral	None	None	None	None	N
Y/N	0.2493	likely_benign	0.2109	benign	-1.063	Destabilizing	0.886	D	0.567	neutral	N	0.514611863	None	None	N
Y/P	0.9915	likely_pathogenic	0.9896	pathogenic	-1.539	Destabilizing	0.987	D	0.577	neutral	None	None	None	None	N
Y/Q	0.4584	ambiguous	0.3875	ambiguous	-1.013	Destabilizing	0.916	D	0.581	neutral	None	None	None	None	N
Y/R	0.4676	ambiguous	0.3992	ambiguous	-0.392	Destabilizing	0.938	D	0.588	neutral	None	None	None	None	N
Y/S	0.2679	likely_benign	0.2241	benign	-1.754	Destabilizing	0.233	N	0.405	neutral	N	0.510807121	None	None	N
Y/T	0.5128	ambiguous	0.4305	ambiguous	-1.568	Destabilizing	0.838	D	0.519	neutral	None	None	None	None	N
Y/V	0.5421	ambiguous	0.4763	ambiguous	-1.539	Destabilizing	0.681	D	0.461	neutral	None	None	None	None	N
Y/W	0.4839	ambiguous	0.4677	ambiguous	-0.437	Destabilizing	0.992	D	0.523	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.