TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26474	79645;79646;79647	chr2:178566712;178566711;178566710	chr2:179431439;179431438;179431437
N2AB	24833	74722;74723;74724	chr2:178566712;178566711;178566710	chr2:179431439;179431438;179431437
N2A	23906	71941;71942;71943	chr2:178566712;178566711;178566710	chr2:179431439;179431438;179431437
N2B	17409	52450;52451;52452	chr2:178566712;178566711;178566710	chr2:179431439;179431438;179431437
Novex-1	17534	52825;52826;52827	chr2:178566712;178566711;178566710	chr2:179431439;179431438;179431437
Novex-2	17601	53026;53027;53028	chr2:178566712;178566711;178566710	chr2:179431439;179431438;179431437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-80
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.7215
• Predicted PPI site: I

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
P/A	rs761511285	-0.277	0.044	N	0.383	0.227	0.207176502487	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
P/A	rs761511285	-0.277	0.044	N	0.383	0.227	0.207176502487	gnomAD-4.0.0	1.23184E-05	None	None	None	None	I	None	5.97764E-05	0	None	0	0	None	0	0	1.43926E-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
P/A	0.051	likely_benign	0.0496	benign	-0.582	Destabilizing	0.044	N	0.383	neutral	N	0.465028319	None	None	I
P/C	0.2526	likely_benign	0.2172	benign	-0.59	Destabilizing	0.96	D	0.564	neutral	None	None	None	None	I
P/D	0.2043	likely_benign	0.1803	benign	-0.114	Destabilizing	0.227	N	0.456	neutral	None	None	None	None	I
P/E	0.1249	likely_benign	0.1166	benign	-0.219	Destabilizing	0.128	N	0.386	neutral	None	None	None	None	I
P/F	0.2357	likely_benign	0.1953	benign	-0.716	Destabilizing	0.507	D	0.503	neutral	None	None	None	None	I
P/G	0.1619	likely_benign	0.1417	benign	-0.738	Destabilizing	0.227	N	0.463	neutral	None	None	None	None	I
P/H	0.1188	likely_benign	0.1102	benign	-0.308	Destabilizing	0.795	D	0.441	neutral	None	None	None	None	I
P/I	0.147	likely_benign	0.1165	benign	-0.318	Destabilizing	0.34	N	0.467	neutral	None	None	None	None	I
P/K	0.1461	likely_benign	0.1366	benign	-0.431	Destabilizing	0.128	N	0.415	neutral	None	None	None	None	I
P/L	0.0636	likely_benign	0.0594	benign	-0.318	Destabilizing	0.001	N	0.462	neutral	N	0.462393446	None	None	I
P/M	0.1377	likely_benign	0.1156	benign	-0.311	Destabilizing	0.507	D	0.482	neutral	None	None	None	None	I
P/N	0.1534	likely_benign	0.1191	benign	-0.147	Destabilizing	0.507	D	0.457	neutral	None	None	None	None	I
P/Q	0.0803	likely_benign	0.0749	benign	-0.386	Destabilizing	None	N	0.187	neutral	N	0.45317653	None	None	I
P/R	0.1183	likely_benign	0.1232	benign	0.06	Stabilizing	0.28	N	0.456	neutral	N	0.470127494	None	None	I
P/S	0.0759	likely_benign	0.0684	benign	-0.57	Destabilizing	0.1	N	0.38	neutral	N	0.462276015	None	None	I
P/T	0.068	likely_benign	0.0594	benign	-0.572	Destabilizing	0.181	N	0.445	neutral	N	0.495465869	None	None	I
P/V	0.0984	likely_benign	0.0862	benign	-0.37	Destabilizing	0.128	N	0.398	neutral	None	None	None	None	I
P/W	0.3644	ambiguous	0.3521	ambiguous	-0.79	Destabilizing	0.96	D	0.611	neutral	None	None	None	None	I
P/Y	0.245	likely_benign	0.2158	benign	-0.49	Destabilizing	0.676	D	0.527	neutral	None	None	None	None	I

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.