TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15219	45880;45881;45882	chr2:178620955;178620954;178620953	chr2:179485682;179485681;179485680
N2AB	13578	40957;40958;40959	chr2:178620955;178620954;178620953	chr2:179485682;179485681;179485680
N2A	12651	38176;38177;38178	chr2:178620955;178620954;178620953	chr2:179485682;179485681;179485680
N2B	6154	18685;18686;18687	chr2:178620955;178620954;178620953	chr2:179485682;179485681;179485680
Novex-1	6279	19060;19061;19062	chr2:178620955;178620954;178620953	chr2:179485682;179485681;179485680
Novex-2	6346	19261;19262;19263	chr2:178620955;178620954;178620953	chr2:179485682;179485681;179485680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-104
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1521
• 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
V/M	rs765315826	-0.654	0.996	D	0.509	0.489	0.666835787278	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
V/M	rs765315826	-0.654	0.996	D	0.509	0.489	0.666835787278	gnomAD-4.0.0	1.59445E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88402E-05	0	0	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
V/A	0.3377	likely_benign	0.2839	benign	-1.932	Destabilizing	0.061	N	0.139	neutral	N	0.49848103	None	None	N
V/C	0.824	likely_pathogenic	0.7916	pathogenic	-1.331	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
V/D	0.8631	likely_pathogenic	0.7259	pathogenic	-2.211	Highly Destabilizing	0.991	D	0.604	neutral	None	None	None	None	N
V/E	0.7112	likely_pathogenic	0.555	ambiguous	-2.141	Highly Destabilizing	0.959	D	0.543	neutral	D	0.671836285	None	None	N
V/F	0.4074	ambiguous	0.2927	benign	-1.286	Destabilizing	0.997	D	0.582	neutral	None	None	None	None	N
V/G	0.3819	ambiguous	0.2852	benign	-2.321	Highly Destabilizing	0.015	N	0.329	neutral	D	0.590975194	None	None	N
V/H	0.91	likely_pathogenic	0.8471	pathogenic	-1.883	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
V/I	0.1086	likely_benign	0.1109	benign	-0.915	Destabilizing	0.927	D	0.455	neutral	None	None	None	None	N
V/K	0.7502	likely_pathogenic	0.6099	pathogenic	-1.79	Destabilizing	0.939	D	0.544	neutral	None	None	None	None	N
V/L	0.4023	ambiguous	0.3464	ambiguous	-0.915	Destabilizing	0.826	D	0.438	neutral	D	0.627263437	None	None	N
V/M	0.2947	likely_benign	0.2561	benign	-0.747	Destabilizing	0.996	D	0.509	neutral	D	0.631578414	None	None	N
V/N	0.7573	likely_pathogenic	0.6371	pathogenic	-1.7	Destabilizing	0.991	D	0.592	neutral	None	None	None	None	N
V/P	0.9651	likely_pathogenic	0.9345	pathogenic	-1.224	Destabilizing	0.991	D	0.552	neutral	None	None	None	None	N
V/Q	0.7037	likely_pathogenic	0.5695	pathogenic	-1.796	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
V/R	0.7171	likely_pathogenic	0.5587	ambiguous	-1.259	Destabilizing	0.991	D	0.597	neutral	None	None	None	None	N
V/S	0.5253	ambiguous	0.437	ambiguous	-2.221	Highly Destabilizing	0.884	D	0.461	neutral	None	None	None	None	N
V/T	0.3622	ambiguous	0.3334	benign	-2.047	Highly Destabilizing	0.939	D	0.437	neutral	None	None	None	None	N
V/W	0.9585	likely_pathogenic	0.9192	pathogenic	-1.606	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
V/Y	0.8672	likely_pathogenic	0.7763	pathogenic	-1.327	Destabilizing	0.997	D	0.568	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.