TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5027	15304;15305;15306	chr2:178734845;178734844;178734843	chr2:179599572;179599571;179599570
N2AB	4710	14353;14354;14355	chr2:178734845;178734844;178734843	chr2:179599572;179599571;179599570
N2A	3783	11572;11573;11574	chr2:178734845;178734844;178734843	chr2:179599572;179599571;179599570
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-33
• Domain position: 47
• Structural Position: 115
• Q(SASA): 0.4277
• 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
T/I	rs778591734	-0.224	0.996	N	0.381	0.287	0.329020015101	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
T/K	None	None	0.061	N	0.187	0.219	0.1749357433	gnomAD-4.0.0	1.36849E-06	None	None	None	None	N	None	0	0	None	0	2.52118E-05	None	0	0	0	0	1.65673E-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
T/A	0.0731	likely_benign	0.0662	benign	-0.493	Destabilizing	0.826	D	0.325	neutral	N	0.445201459	None	None	N
T/C	0.3975	ambiguous	0.3592	ambiguous	-0.222	Destabilizing	0.999	D	0.371	neutral	None	None	None	None	N
T/D	0.2757	likely_benign	0.2299	benign	-0.003	Destabilizing	0.969	D	0.383	neutral	None	None	None	None	N
T/E	0.2391	likely_benign	0.2071	benign	-0.078	Destabilizing	0.939	D	0.322	neutral	None	None	None	None	N
T/F	0.2244	likely_benign	0.1828	benign	-0.947	Destabilizing	0.997	D	0.383	neutral	None	None	None	None	N
T/G	0.2011	likely_benign	0.1694	benign	-0.637	Destabilizing	0.969	D	0.351	neutral	None	None	None	None	N
T/H	0.1621	likely_benign	0.1528	benign	-1.032	Destabilizing	0.997	D	0.381	neutral	None	None	None	None	N
T/I	0.1732	likely_benign	0.1411	benign	-0.228	Destabilizing	0.996	D	0.381	neutral	N	0.444821645	None	None	N
T/K	0.1088	likely_benign	0.1179	benign	-0.464	Destabilizing	0.061	N	0.187	neutral	N	0.33178327	None	None	N
T/L	0.1029	likely_benign	0.0917	benign	-0.228	Destabilizing	0.969	D	0.328	neutral	None	None	None	None	N
T/M	0.088	likely_benign	0.0853	benign	0.129	Stabilizing	0.997	D	0.35	neutral	None	None	None	None	N
T/N	0.1044	likely_benign	0.088	benign	-0.205	Destabilizing	0.969	D	0.383	neutral	None	None	None	None	N
T/P	0.2564	likely_benign	0.1984	benign	-0.288	Destabilizing	0.996	D	0.382	neutral	N	0.443407242	None	None	N
T/Q	0.1616	likely_benign	0.1564	benign	-0.489	Destabilizing	0.982	D	0.375	neutral	None	None	None	None	N
T/R	0.09	likely_benign	0.0959	benign	-0.182	Destabilizing	0.035	N	0.235	neutral	N	0.370858071	None	None	N
T/S	0.096	likely_benign	0.0813	benign	-0.422	Destabilizing	0.826	D	0.383	neutral	N	0.427035118	None	None	N
T/V	0.1402	likely_benign	0.117	benign	-0.288	Destabilizing	0.969	D	0.329	neutral	None	None	None	None	N
T/W	0.5025	ambiguous	0.4469	ambiguous	-0.913	Destabilizing	0.999	D	0.469	neutral	None	None	None	None	N
T/Y	0.2305	likely_benign	0.1932	benign	-0.652	Destabilizing	0.997	D	0.378	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.