TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8770	26533;26534;26535	chr2:178714466;178714465;178714464	chr2:179579193;179579192;179579191
N2AB	8453	25582;25583;25584	chr2:178714466;178714465;178714464	chr2:179579193;179579192;179579191
N2A	7526	22801;22802;22803	chr2:178714466;178714465;178714464	chr2:179579193;179579192;179579191
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-73
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1393
• 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
F/S	None	None	0.844	N	0.53	0.346	0.575814496085	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85892E-06	0	0
F/V	rs2077156183	None	0.002	N	0.251	0.203	0.447901950027	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
F/V	rs2077156183	None	0.002	N	0.251	0.203	0.447901950027	gnomAD-4.0.0	6.57324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07211E-04	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
F/A	0.3896	ambiguous	0.6068	pathogenic	-2.734	Highly Destabilizing	0.39	N	0.455	neutral	None	None	None	None	N
F/C	0.1962	likely_benign	0.3361	benign	-1.548	Destabilizing	0.983	D	0.583	neutral	N	0.496525888	None	None	N
F/D	0.7026	likely_pathogenic	0.8631	pathogenic	-2.178	Highly Destabilizing	0.956	D	0.645	neutral	None	None	None	None	N
F/E	0.5885	likely_pathogenic	0.7749	pathogenic	-2.042	Highly Destabilizing	0.868	D	0.594	neutral	None	None	None	None	N
F/G	0.5806	likely_pathogenic	0.766	pathogenic	-3.116	Highly Destabilizing	0.878	D	0.559	neutral	None	None	None	None	N
F/H	0.3234	likely_benign	0.4626	ambiguous	-1.38	Destabilizing	0.883	D	0.563	neutral	None	None	None	None	N
F/I	0.1108	likely_benign	0.1678	benign	-1.531	Destabilizing	0.091	N	0.383	neutral	N	0.503367703	None	None	N
F/K	0.4684	ambiguous	0.6512	pathogenic	-1.574	Destabilizing	0.749	D	0.596	neutral	None	None	None	None	N
F/L	0.3427	ambiguous	0.5354	ambiguous	-1.531	Destabilizing	None	N	0.185	neutral	N	0.41051347	None	None	N
F/M	0.2225	likely_benign	0.3095	benign	-1.244	Destabilizing	0.005	N	0.369	neutral	None	None	None	None	N
F/N	0.4136	ambiguous	0.5974	pathogenic	-1.729	Destabilizing	0.987	D	0.645	neutral	None	None	None	None	N
F/P	0.9841	likely_pathogenic	0.996	pathogenic	-1.935	Destabilizing	0.987	D	0.639	neutral	None	None	None	None	N
F/Q	0.3723	ambiguous	0.5702	pathogenic	-1.825	Destabilizing	0.883	D	0.645	neutral	None	None	None	None	N
F/R	0.3606	ambiguous	0.5342	ambiguous	-0.904	Destabilizing	0.749	D	0.65	neutral	None	None	None	None	N
F/S	0.2968	likely_benign	0.4856	ambiguous	-2.508	Highly Destabilizing	0.844	D	0.53	neutral	N	0.509466956	None	None	N
F/T	0.3605	ambiguous	0.5392	ambiguous	-2.277	Highly Destabilizing	0.594	D	0.487	neutral	None	None	None	None	N
F/V	0.1256	likely_benign	0.1934	benign	-1.935	Destabilizing	0.002	N	0.251	neutral	N	0.495017578	None	None	N
F/W	0.2442	likely_benign	0.3506	ambiguous	-0.42	Destabilizing	0.977	D	0.551	neutral	None	None	None	None	N
F/Y	0.1023	likely_benign	0.1199	benign	-0.73	Destabilizing	0.003	N	0.216	neutral	N	0.443836609	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.