TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28338	85237;85238;85239	chr2:178561120;178561119;178561118	chr2:179425847;179425846;179425845
N2AB	26697	80314;80315;80316	chr2:178561120;178561119;178561118	chr2:179425847;179425846;179425845
N2A	25770	77533;77534;77535	chr2:178561120;178561119;178561118	chr2:179425847;179425846;179425845
N2B	19273	58042;58043;58044	chr2:178561120;178561119;178561118	chr2:179425847;179425846;179425845
Novex-1	19398	58417;58418;58419	chr2:178561120;178561119;178561118	chr2:179425847;179425846;179425845
Novex-2	19465	58618;58619;58620	chr2:178561120;178561119;178561118	chr2:179425847;179425846;179425845
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: Fn3-94
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6008
• 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
E/D	None	None	0.801	N	0.327	0.137	0.187945064343	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85798E-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	0.1074	likely_benign	0.1024	benign	-0.669	Destabilizing	0.022	N	0.183	neutral	N	0.498490319	None	None	N
E/C	0.6928	likely_pathogenic	0.7084	pathogenic	-0.433	Destabilizing	0.998	D	0.341	neutral	None	None	None	None	N
E/D	0.1161	likely_benign	0.1237	benign	-0.61	Destabilizing	0.801	D	0.327	neutral	N	0.511035541	None	None	N
E/F	0.5829	likely_pathogenic	0.5745	pathogenic	-0.164	Destabilizing	0.974	D	0.379	neutral	None	None	None	None	N
E/G	0.1416	likely_benign	0.1299	benign	-0.927	Destabilizing	0.801	D	0.369	neutral	N	0.490447318	None	None	N
E/H	0.3647	ambiguous	0.3463	ambiguous	0.168	Stabilizing	0.974	D	0.421	neutral	None	None	None	None	N
E/I	0.2227	likely_benign	0.2158	benign	0.005	Stabilizing	0.728	D	0.433	neutral	None	None	None	None	N
E/K	0.0916	likely_benign	0.0849	benign	-0.009	Destabilizing	0.454	N	0.309	neutral	N	0.497316883	None	None	N
E/L	0.2136	likely_benign	0.2071	benign	0.005	Stabilizing	0.525	D	0.387	neutral	None	None	None	None	N
E/M	0.2904	likely_benign	0.2827	benign	0.081	Stabilizing	0.974	D	0.354	neutral	None	None	None	None	N
E/N	0.1916	likely_benign	0.1964	benign	-0.606	Destabilizing	0.842	D	0.423	neutral	None	None	None	None	N
E/P	0.2756	likely_benign	0.2559	benign	-0.2	Destabilizing	0.016	N	0.223	neutral	None	None	None	None	N
E/Q	0.1062	likely_benign	0.0964	benign	-0.51	Destabilizing	0.051	N	0.138	neutral	N	0.475078541	None	None	N
E/R	0.1758	likely_benign	0.1568	benign	0.41	Stabilizing	0.728	D	0.4	neutral	None	None	None	None	N
E/S	0.1562	likely_benign	0.147	benign	-0.771	Destabilizing	0.525	D	0.327	neutral	None	None	None	None	N
E/T	0.1882	likely_benign	0.1733	benign	-0.543	Destabilizing	0.842	D	0.37	neutral	None	None	None	None	N
E/V	0.1406	likely_benign	0.1346	benign	-0.2	Destabilizing	0.051	N	0.273	neutral	N	0.472560553	None	None	N
E/W	0.8295	likely_pathogenic	0.815	pathogenic	0.134	Stabilizing	0.998	D	0.421	neutral	None	None	None	None	N
E/Y	0.4419	ambiguous	0.4425	ambiguous	0.11	Stabilizing	0.991	D	0.385	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.