TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18152	54679;54680;54681	chr2:178604233;178604232;178604231	chr2:179468960;179468959;179468958
N2AB	16511	49756;49757;49758	chr2:178604233;178604232;178604231	chr2:179468960;179468959;179468958
N2A	15584	46975;46976;46977	chr2:178604233;178604232;178604231	chr2:179468960;179468959;179468958
N2B	9087	27484;27485;27486	chr2:178604233;178604232;178604231	chr2:179468960;179468959;179468958
Novex-1	9212	27859;27860;27861	chr2:178604233;178604232;178604231	chr2:179468960;179468959;179468958
Novex-2	9279	28060;28061;28062	chr2:178604233;178604232;178604231	chr2:179468960;179468959;179468958
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: Fn3-19
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.2963
• 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	0.007	N	0.231	0.03	0.0551355673512	gnomAD-4.0.0	6.90601E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05487E-07	0	0
E/K	None	None	0.684	N	0.437	0.222	0.218845423259	gnomAD-4.0.0	1.38499E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.07342E-07	0	1.67949E-05

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	0.1224	likely_benign	0.1251	benign	-0.793	Destabilizing	0.028	N	0.324	neutral	N	0.372078086	None	None	N
E/C	0.7766	likely_pathogenic	0.7579	pathogenic	-0.476	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
E/D	0.1	likely_benign	0.084	benign	-1.048	Destabilizing	0.007	N	0.231	neutral	N	0.459467784	None	None	N
E/F	0.7038	likely_pathogenic	0.6331	pathogenic	-0.334	Destabilizing	0.984	D	0.593	neutral	None	None	None	None	N
E/G	0.1832	likely_benign	0.1656	benign	-1.117	Destabilizing	0.003	N	0.434	neutral	N	0.422296262	None	None	N
E/H	0.5726	likely_pathogenic	0.5261	ambiguous	-0.496	Destabilizing	0.984	D	0.529	neutral	None	None	None	None	N
E/I	0.446	ambiguous	0.3537	ambiguous	0.078	Stabilizing	0.953	D	0.605	neutral	None	None	None	None	N
E/K	0.4435	ambiguous	0.3679	ambiguous	-0.647	Destabilizing	0.684	D	0.437	neutral	N	0.458947709	None	None	N
E/L	0.6177	likely_pathogenic	0.5152	ambiguous	0.078	Stabilizing	0.742	D	0.557	neutral	None	None	None	None	N
E/M	0.6074	likely_pathogenic	0.5336	ambiguous	0.412	Stabilizing	0.996	D	0.606	neutral	None	None	None	None	N
E/N	0.3124	likely_benign	0.251	benign	-1.004	Destabilizing	0.59	D	0.436	neutral	None	None	None	None	N
E/P	0.3104	likely_benign	0.3181	benign	-0.192	Destabilizing	0.004	N	0.324	neutral	None	None	None	None	N
E/Q	0.2706	likely_benign	0.2519	benign	-0.906	Destabilizing	0.815	D	0.462	neutral	N	0.477533469	None	None	N
E/R	0.6056	likely_pathogenic	0.5346	ambiguous	-0.298	Destabilizing	0.953	D	0.497	neutral	None	None	None	None	N
E/S	0.1753	likely_benign	0.1727	benign	-1.272	Destabilizing	0.373	N	0.416	neutral	None	None	None	None	N
E/T	0.2708	likely_benign	0.2355	benign	-1.017	Destabilizing	0.742	D	0.49	neutral	None	None	None	None	N
E/V	0.2958	likely_benign	0.2423	benign	-0.192	Destabilizing	0.684	D	0.539	neutral	N	0.477013394	None	None	N
E/W	0.905	likely_pathogenic	0.8779	pathogenic	-0.112	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	N
E/Y	0.5503	ambiguous	0.4734	ambiguous	-0.107	Destabilizing	0.984	D	0.6	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.