TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9403	28432;28433;28434	chr2:178710890;178710889;178710888	chr2:179575617;179575616;179575615
N2AB	9086	27481;27482;27483	chr2:178710890;178710889;178710888	chr2:179575617;179575616;179575615
N2A	8159	24700;24701;24702	chr2:178710890;178710889;178710888	chr2:179575617;179575616;179575615
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-80
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1225
• 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
L/V	rs752742472	-1.449	None	None	0.435	0.082	0.0716867268079	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
L/V	rs752742472	-1.449	None	None	0.435	0.082	0.0716867268079	gnomAD-4.0.0	2.73738E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63811E-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
L/A	0.1405	likely_benign	0.1782	benign	-2.362	Highly Destabilizing	0.035	N	0.579	neutral	None	None	None	None	N
L/C	0.5637	ambiguous	0.6023	pathogenic	-1.441	Destabilizing	0.824	D	0.633	neutral	None	None	None	None	N
L/D	0.8854	likely_pathogenic	0.9279	pathogenic	-2.108	Highly Destabilizing	0.38	N	0.73	prob.delet.	None	None	None	None	N
L/E	0.6794	likely_pathogenic	0.7407	pathogenic	-1.958	Destabilizing	0.38	N	0.723	prob.delet.	None	None	None	None	N
L/F	0.3713	ambiguous	0.4448	ambiguous	-1.414	Destabilizing	0.317	N	0.646	neutral	None	None	None	None	N
L/G	0.5059	ambiguous	0.5963	pathogenic	-2.852	Highly Destabilizing	0.38	N	0.725	prob.delet.	None	None	None	None	N
L/H	0.6255	likely_pathogenic	0.7199	pathogenic	-2.142	Highly Destabilizing	0.915	D	0.694	prob.neutral	None	None	None	None	N
L/I	0.0913	likely_benign	0.1034	benign	-0.985	Destabilizing	None	N	0.209	neutral	None	None	None	None	N
L/K	0.6967	likely_pathogenic	0.7739	pathogenic	-1.708	Destabilizing	0.38	N	0.685	prob.neutral	None	None	None	None	N
L/M	0.1484	likely_benign	0.1791	benign	-0.761	Destabilizing	0.38	N	0.57	neutral	None	None	None	None	N
L/N	0.559	ambiguous	0.685	pathogenic	-1.763	Destabilizing	0.38	N	0.732	prob.delet.	None	None	None	None	N
L/P	0.0921	likely_benign	0.1123	benign	-1.42	Destabilizing	None	N	0.556	neutral	None	None	None	None	N
L/Q	0.4636	ambiguous	0.533	ambiguous	-1.746	Destabilizing	0.555	D	0.654	neutral	None	None	None	None	N
L/R	0.6249	likely_pathogenic	0.7004	pathogenic	-1.295	Destabilizing	0.317	N	0.684	prob.neutral	None	None	None	None	N
L/S	0.3743	ambiguous	0.4657	ambiguous	-2.495	Highly Destabilizing	0.081	N	0.65	neutral	None	None	None	None	N
L/T	0.1996	likely_benign	0.2411	benign	-2.208	Highly Destabilizing	0.001	N	0.479	neutral	None	None	None	None	N
L/V	0.0923	likely_benign	0.0928	benign	-1.42	Destabilizing	None	N	0.435	neutral	None	None	None	None	N
L/W	0.7063	likely_pathogenic	0.7535	pathogenic	-1.685	Destabilizing	0.935	D	0.67	neutral	None	None	None	None	N
L/Y	0.7477	likely_pathogenic	0.8156	pathogenic	-1.434	Destabilizing	0.555	D	0.671	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.