TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26340	79243;79244;79245	chr2:178567114;178567113;178567112	chr2:179431841;179431840;179431839
N2AB	24699	74320;74321;74322	chr2:178567114;178567113;178567112	chr2:179431841;179431840;179431839
N2A	23772	71539;71540;71541	chr2:178567114;178567113;178567112	chr2:179431841;179431840;179431839
N2B	17275	52048;52049;52050	chr2:178567114;178567113;178567112	chr2:179431841;179431840;179431839
Novex-1	17400	52423;52424;52425	chr2:178567114;178567113;178567112	chr2:179431841;179431840;179431839
Novex-2	17467	52624;52625;52626	chr2:178567114;178567113;178567112	chr2:179431841;179431840;179431839
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-79
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.5793
• 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
E/Q	None	None	0.684	N	0.325	0.107	0.177238962908	gnomAD-4.0.0	6.84306E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99583E-07	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
E/A	0.1781	likely_benign	0.1611	benign	-0.399	Destabilizing	0.028	N	0.142	neutral	N	0.463935028	None	None	I
E/C	0.8523	likely_pathogenic	0.8071	pathogenic	-0.136	Destabilizing	0.996	D	0.245	neutral	None	None	None	None	I
E/D	0.0969	likely_benign	0.0826	benign	-0.293	Destabilizing	0.007	N	0.1	neutral	N	0.407406954	None	None	I
E/F	0.8241	likely_pathogenic	0.7772	pathogenic	-0.244	Destabilizing	0.953	D	0.285	neutral	None	None	None	None	I
E/G	0.1959	likely_benign	0.1594	benign	-0.603	Destabilizing	0.309	N	0.32	neutral	N	0.452256597	None	None	I
E/H	0.4415	ambiguous	0.3785	ambiguous	0.026	Stabilizing	0.953	D	0.34	neutral	None	None	None	None	I
E/I	0.5283	ambiguous	0.4869	ambiguous	0.107	Stabilizing	0.59	D	0.323	neutral	None	None	None	None	I
E/K	0.2098	likely_benign	0.1824	benign	0.173	Stabilizing	0.684	D	0.266	neutral	N	0.449061576	None	None	I
E/L	0.5367	ambiguous	0.4861	ambiguous	0.107	Stabilizing	0.59	D	0.343	neutral	None	None	None	None	I
E/M	0.5556	ambiguous	0.5123	ambiguous	0.156	Stabilizing	0.953	D	0.258	neutral	None	None	None	None	I
E/N	0.1612	likely_benign	0.1416	benign	-0.088	Destabilizing	0.009	N	0.15	neutral	None	None	None	None	I
E/P	0.7805	likely_pathogenic	0.7164	pathogenic	-0.042	Destabilizing	0.953	D	0.359	neutral	None	None	None	None	I
E/Q	0.1624	likely_benign	0.151	benign	-0.049	Destabilizing	0.684	D	0.325	neutral	N	0.474498738	None	None	I
E/R	0.3453	ambiguous	0.2992	benign	0.443	Stabilizing	0.91	D	0.335	neutral	None	None	None	None	I
E/S	0.1708	likely_benign	0.1489	benign	-0.289	Destabilizing	0.373	N	0.266	neutral	None	None	None	None	I
E/T	0.2207	likely_benign	0.1982	benign	-0.127	Destabilizing	0.742	D	0.323	neutral	None	None	None	None	I
E/V	0.3108	likely_benign	0.2875	benign	-0.042	Destabilizing	0.012	N	0.163	neutral	N	0.478115046	None	None	I
E/W	0.939	likely_pathogenic	0.9066	pathogenic	-0.092	Destabilizing	0.996	D	0.402	neutral	None	None	None	None	I
E/Y	0.6794	likely_pathogenic	0.6022	pathogenic	-0.008	Destabilizing	0.984	D	0.277	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.