TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9253	27982;27983;27984	chr2:178712073;178712072;178712071	chr2:179576800;179576799;179576798
N2AB	8936	27031;27032;27033	chr2:178712073;178712072;178712071	chr2:179576800;179576799;179576798
N2A	8009	24250;24251;24252	chr2:178712073;178712072;178712071	chr2:179576800;179576799;179576798
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-78
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2166
• 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
M/I	rs1477695783	-0.791	0.002	N	0.111	0.159	0.467501455318	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
M/I	rs1477695783	-0.791	0.002	N	0.111	0.159	0.467501455318	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
M/I	rs1477695783	-0.791	0.002	N	0.111	0.159	0.467501455318	gnomAD-4.0.0	2.03E-06	None	None	None	None	N	None	3.49638E-05	0	None	0	0	None	0	0	0	0	0
M/T	None	None	0.642	N	0.429	0.413	0.786132194152	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	None	0	0	0	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
M/A	0.6994	likely_pathogenic	0.769	pathogenic	-2.907	Highly Destabilizing	0.495	N	0.357	neutral	None	None	None	None	N
M/C	0.9009	likely_pathogenic	0.9099	pathogenic	-1.757	Destabilizing	0.981	D	0.506	neutral	None	None	None	None	N
M/D	0.9599	likely_pathogenic	0.9675	pathogenic	-1.84	Destabilizing	0.981	D	0.615	neutral	None	None	None	None	N
M/E	0.7958	likely_pathogenic	0.8349	pathogenic	-1.71	Destabilizing	0.936	D	0.547	neutral	None	None	None	None	N
M/F	0.4449	ambiguous	0.5557	ambiguous	-1.449	Destabilizing	0.704	D	0.371	neutral	None	None	None	None	N
M/G	0.8688	likely_pathogenic	0.8995	pathogenic	-3.301	Highly Destabilizing	0.936	D	0.571	neutral	None	None	None	None	N
M/H	0.8123	likely_pathogenic	0.8508	pathogenic	-2.454	Highly Destabilizing	0.995	D	0.551	neutral	None	None	None	None	N
M/I	0.3538	ambiguous	0.4363	ambiguous	-1.788	Destabilizing	0.002	N	0.111	neutral	N	0.437394293	None	None	N
M/K	0.4766	ambiguous	0.5647	pathogenic	-1.695	Destabilizing	0.784	D	0.449	neutral	N	0.491265872	None	None	N
M/L	0.1948	likely_benign	0.2578	benign	-1.788	Destabilizing	0.001	N	0.088	neutral	N	0.473355093	None	None	N
M/N	0.7507	likely_pathogenic	0.7749	pathogenic	-1.664	Destabilizing	0.981	D	0.586	neutral	None	None	None	None	N
M/P	0.9275	likely_pathogenic	0.9516	pathogenic	-2.144	Highly Destabilizing	0.981	D	0.586	neutral	None	None	None	None	N
M/Q	0.5107	ambiguous	0.5362	ambiguous	-1.602	Destabilizing	0.981	D	0.457	neutral	None	None	None	None	N
M/R	0.5064	ambiguous	0.6313	pathogenic	-1.306	Destabilizing	0.917	D	0.55	neutral	N	0.484771412	None	None	N
M/S	0.7052	likely_pathogenic	0.7518	pathogenic	-2.284	Highly Destabilizing	0.828	D	0.427	neutral	None	None	None	None	N
M/T	0.4074	ambiguous	0.4167	ambiguous	-2.052	Highly Destabilizing	0.642	D	0.429	neutral	N	0.471221652	None	None	N
M/V	0.1517	likely_benign	0.1901	benign	-2.144	Highly Destabilizing	0.065	N	0.28	neutral	N	0.443568116	None	None	N
M/W	0.8042	likely_pathogenic	0.8912	pathogenic	-1.485	Destabilizing	0.995	D	0.493	neutral	None	None	None	None	N
M/Y	0.6963	likely_pathogenic	0.7974	pathogenic	-1.646	Destabilizing	0.981	D	0.534	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.