TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17001	51226;51227;51228	chr2:178611128;178611127;178611126	chr2:179475855;179475854;179475853
N2AB	15360	46303;46304;46305	chr2:178611128;178611127;178611126	chr2:179475855;179475854;179475853
N2A	14433	43522;43523;43524	chr2:178611128;178611127;178611126	chr2:179475855;179475854;179475853
N2B	7936	24031;24032;24033	chr2:178611128;178611127;178611126	chr2:179475855;179475854;179475853
Novex-1	8061	24406;24407;24408	chr2:178611128;178611127;178611126	chr2:179475855;179475854;179475853
Novex-2	8128	24607;24608;24609	chr2:178611128;178611127;178611126	chr2:179475855;179475854;179475853
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-111
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1809
• 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
L/F	None	None	0.655	N	0.527	0.084	0.344483371355	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.4124	ambiguous	0.4847	ambiguous	-1.784	Destabilizing	0.004	N	0.252	neutral	None	None	None	None	N
L/C	0.4929	ambiguous	0.5326	ambiguous	-1.17	Destabilizing	0.94	D	0.564	neutral	None	None	None	None	N
L/D	0.898	likely_pathogenic	0.9104	pathogenic	-1.208	Destabilizing	0.418	N	0.594	neutral	None	None	None	None	N
L/E	0.642	likely_pathogenic	0.6905	pathogenic	-1.196	Destabilizing	0.418	N	0.576	neutral	None	None	None	None	N
L/F	0.1592	likely_benign	0.1904	benign	-1.284	Destabilizing	0.655	D	0.527	neutral	N	0.500624633	None	None	N
L/G	0.7392	likely_pathogenic	0.7769	pathogenic	-2.128	Highly Destabilizing	0.228	N	0.517	neutral	None	None	None	None	N
L/H	0.4379	ambiguous	0.4965	ambiguous	-1.38	Destabilizing	0.94	D	0.589	neutral	None	None	None	None	N
L/I	0.0825	likely_benign	0.096	benign	-0.903	Destabilizing	0.002	N	0.151	neutral	N	0.478166859	None	None	N
L/K	0.5508	ambiguous	0.5901	pathogenic	-1.261	Destabilizing	0.418	N	0.537	neutral	None	None	None	None	N
L/M	0.1139	likely_benign	0.1271	benign	-0.712	Destabilizing	0.716	D	0.533	neutral	None	None	None	None	N
L/N	0.6346	likely_pathogenic	0.6934	pathogenic	-1.071	Destabilizing	0.418	N	0.591	neutral	None	None	None	None	N
L/P	0.9152	likely_pathogenic	0.9122	pathogenic	-1.166	Destabilizing	0.593	D	0.615	neutral	None	None	None	None	N
L/Q	0.3593	ambiguous	0.4068	ambiguous	-1.237	Destabilizing	0.836	D	0.596	neutral	None	None	None	None	N
L/R	0.4917	ambiguous	0.5363	ambiguous	-0.683	Destabilizing	0.716	D	0.587	neutral	None	None	None	None	N
L/S	0.5118	ambiguous	0.6102	pathogenic	-1.711	Destabilizing	0.021	N	0.358	neutral	N	0.513981447	None	None	N
L/T	0.2984	likely_benign	0.3636	ambiguous	-1.577	Destabilizing	0.001	N	0.25	neutral	None	None	None	None	N
L/V	0.0903	likely_benign	0.0973	benign	-1.166	Destabilizing	0.001	N	0.161	neutral	N	0.454255523	None	None	N
L/W	0.3929	ambiguous	0.4188	ambiguous	-1.356	Destabilizing	0.983	D	0.569	neutral	None	None	None	None	N
L/Y	0.4449	ambiguous	0.4973	ambiguous	-1.138	Destabilizing	0.836	D	0.563	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.