TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19274	58045;58046;58047	chr2:178595534;178595533;178595532	chr2:179460261;179460260;179460259
N2AB	17633	53122;53123;53124	chr2:178595534;178595533;178595532	chr2:179460261;179460260;179460259
N2A	16706	50341;50342;50343	chr2:178595534;178595533;178595532	chr2:179460261;179460260;179460259
N2B	10209	30850;30851;30852	chr2:178595534;178595533;178595532	chr2:179460261;179460260;179460259
Novex-1	10334	31225;31226;31227	chr2:178595534;178595533;178595532	chr2:179460261;179460260;179460259
Novex-2	10401	31426;31427;31428	chr2:178595534;178595533;178595532	chr2:179460261;179460260;179460259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-27
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.7595
• 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/K	rs1410177303	None	None	N	0.035	0.135	0.0401082797425	gnomAD-4.0.0	1.41807E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.84462E-06	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	0.1059	likely_benign	0.1218	benign	-0.022	Destabilizing	None	N	0.085	neutral	N	0.437553716	None	None	I
E/C	0.5256	ambiguous	0.6339	pathogenic	-0.306	Destabilizing	0.131	N	0.181	neutral	None	None	None	None	I
E/D	0.0797	likely_benign	0.0868	benign	-0.337	Destabilizing	None	N	0.079	neutral	N	0.450272297	None	None	I
E/F	0.5275	ambiguous	0.665	pathogenic	0.006	Stabilizing	0.041	N	0.457	neutral	None	None	None	None	I
E/G	0.1199	likely_benign	0.1503	benign	-0.134	Destabilizing	0.001	N	0.179	neutral	N	0.476400106	None	None	I
E/H	0.2026	likely_benign	0.2623	benign	0.678	Stabilizing	None	N	0.062	neutral	None	None	None	None	I
E/I	0.2544	likely_benign	0.3136	benign	0.219	Stabilizing	0.01	N	0.489	neutral	None	None	None	None	I
E/K	0.0828	likely_benign	0.1027	benign	0.395	Stabilizing	None	N	0.035	neutral	N	0.45225381	None	None	I
E/L	0.2666	likely_benign	0.3442	ambiguous	0.219	Stabilizing	0.004	N	0.215	neutral	None	None	None	None	I
E/M	0.3072	likely_benign	0.3757	ambiguous	-0.064	Destabilizing	0.131	N	0.277	neutral	None	None	None	None	I
E/N	0.1064	likely_benign	0.1245	benign	0.046	Stabilizing	None	N	0.039	neutral	None	None	None	None	I
E/P	0.5242	ambiguous	0.6214	pathogenic	0.156	Stabilizing	0.017	N	0.281	neutral	None	None	None	None	I
E/Q	0.0936	likely_benign	0.1023	benign	0.077	Stabilizing	None	N	0.095	neutral	N	0.48773182	None	None	I
E/R	0.1337	likely_benign	0.1734	benign	0.66	Stabilizing	0.004	N	0.145	neutral	None	None	None	None	I
E/S	0.1071	likely_benign	0.123	benign	-0.065	Destabilizing	0.001	N	0.104	neutral	None	None	None	None	I
E/T	0.115	likely_benign	0.1348	benign	0.044	Stabilizing	None	N	0.079	neutral	None	None	None	None	I
E/V	0.1586	likely_benign	0.19	benign	0.156	Stabilizing	0.003	N	0.179	neutral	N	0.462892091	None	None	I
E/W	0.7411	likely_pathogenic	0.842	pathogenic	0.067	Stabilizing	0.633	D	0.173	neutral	None	None	None	None	I
E/Y	0.3555	ambiguous	0.4736	ambiguous	0.23	Stabilizing	0.021	N	0.407	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.