TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8178	24757;24758;24759	chr2:178718574;178718573;178718572	chr2:179583301;179583300;179583299
N2AB	7861	23806;23807;23808	chr2:178718574;178718573;178718572	chr2:179583301;179583300;179583299
N2A	6934	21025;21026;21027	chr2:178718574;178718573;178718572	chr2:179583301;179583300;179583299
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-67
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3604
• 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
A/S	rs1164648572	-0.479	0.001	N	0.087	0.052	0.0920862733494	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
A/S	rs1164648572	-0.479	0.001	N	0.087	0.052	0.0920862733494	gnomAD-4.0.0	3.18901E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86512E-06	1.43521E-05	0
A/V	None	None	None	N	0.063	0.132	0.262175524916	gnomAD-4.0.0	6.16271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.10071E-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
A/C	0.481	ambiguous	0.4969	ambiguous	-0.852	Destabilizing	0.667	D	0.378	neutral	None	None	None	None	N
A/D	0.2112	likely_benign	0.2222	benign	-0.439	Destabilizing	0.096	N	0.453	neutral	N	0.478531626	None	None	N
A/E	0.2074	likely_benign	0.2142	benign	-0.571	Destabilizing	0.22	N	0.419	neutral	None	None	None	None	N
A/F	0.3456	ambiguous	0.3727	ambiguous	-0.807	Destabilizing	0.497	N	0.479	neutral	None	None	None	None	N
A/G	0.1145	likely_benign	0.1217	benign	-0.326	Destabilizing	0.042	N	0.261	neutral	N	0.491884925	None	None	N
A/H	0.3817	ambiguous	0.4015	ambiguous	-0.319	Destabilizing	0.667	D	0.434	neutral	None	None	None	None	N
A/I	0.2336	likely_benign	0.2483	benign	-0.279	Destabilizing	0.004	N	0.165	neutral	None	None	None	None	N
A/K	0.3335	likely_benign	0.3583	ambiguous	-0.656	Destabilizing	0.22	N	0.42	neutral	None	None	None	None	N
A/L	0.1539	likely_benign	0.1628	benign	-0.279	Destabilizing	0.055	N	0.346	neutral	None	None	None	None	N
A/M	0.2153	likely_benign	0.2217	benign	-0.502	Destabilizing	0.667	D	0.411	neutral	None	None	None	None	N
A/N	0.1652	likely_benign	0.1801	benign	-0.369	Destabilizing	0.001	N	0.21	neutral	None	None	None	None	N
A/P	0.2074	likely_benign	0.2453	benign	-0.241	Destabilizing	0.301	N	0.454	neutral	N	0.454713404	None	None	N
A/Q	0.2588	likely_benign	0.2751	benign	-0.598	Destabilizing	0.667	D	0.46	neutral	None	None	None	None	N
A/R	0.2915	likely_benign	0.3178	benign	-0.231	Destabilizing	0.22	N	0.48	neutral	None	None	None	None	N
A/S	0.0818	likely_benign	0.0835	benign	-0.582	Destabilizing	0.001	N	0.087	neutral	N	0.412671993	None	None	N
A/T	0.0754	likely_benign	0.0777	benign	-0.626	Destabilizing	None	N	0.08	neutral	N	0.420888832	None	None	N
A/V	0.1211	likely_benign	0.1264	benign	-0.241	Destabilizing	None	N	0.063	neutral	N	0.491711567	None	None	N
A/W	0.667	likely_pathogenic	0.6901	pathogenic	-0.96	Destabilizing	0.958	D	0.461	neutral	None	None	None	None	N
A/Y	0.4263	ambiguous	0.4516	ambiguous	-0.61	Destabilizing	0.667	D	0.465	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.