TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6893	20902;20903;20904	chr2:178725527;178725526;178725525	chr2:179590254;179590253;179590252
N2AB	6576	19951;19952;19953	chr2:178725527;178725526;178725525	chr2:179590254;179590253;179590252
N2A	5649	17170;17171;17172	chr2:178725527;178725526;178725525	chr2:179590254;179590253;179590252
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-53
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.3371
• 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/G	rs2079188744	None	0.722	N	0.401	0.323	0.421674004627	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs2079188744	None	0.722	N	0.401	0.323	0.421674004627	gnomAD-4.0.0	6.57194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47042E-05	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
E/A	0.1142	likely_benign	0.1394	benign	-0.69	Destabilizing	0.722	D	0.377	neutral	N	0.495202664	None	None	N
E/C	0.7972	likely_pathogenic	0.849	pathogenic	-0.382	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
E/D	0.0884	likely_benign	0.0826	benign	-0.678	Destabilizing	0.008	N	0.161	neutral	N	0.487822831	None	None	N
E/F	0.6296	likely_pathogenic	0.7114	pathogenic	-0.09	Destabilizing	0.961	D	0.553	neutral	None	None	None	None	N
E/G	0.1324	likely_benign	0.1691	benign	-1.0	Destabilizing	0.722	D	0.401	neutral	N	0.508333396	None	None	N
E/H	0.4546	ambiguous	0.5295	ambiguous	-0.014	Destabilizing	0.011	N	0.201	neutral	None	None	None	None	N
E/I	0.2956	likely_benign	0.3294	benign	0.136	Stabilizing	0.961	D	0.553	neutral	None	None	None	None	N
E/K	0.1848	likely_benign	0.2479	benign	-0.095	Destabilizing	0.722	D	0.393	neutral	N	0.488401808	None	None	N
E/L	0.3309	likely_benign	0.4041	ambiguous	0.136	Stabilizing	0.961	D	0.449	neutral	None	None	None	None	N
E/M	0.3967	ambiguous	0.4423	ambiguous	0.304	Stabilizing	0.996	D	0.54	neutral	None	None	None	None	N
E/N	0.1785	likely_benign	0.2012	benign	-0.728	Destabilizing	0.633	D	0.337	neutral	None	None	None	None	N
E/P	0.4359	ambiguous	0.6693	pathogenic	-0.118	Destabilizing	0.961	D	0.427	neutral	None	None	None	None	N
E/Q	0.1731	likely_benign	0.204	benign	-0.609	Destabilizing	0.722	D	0.396	neutral	N	0.496137262	None	None	N
E/R	0.3219	likely_benign	0.4203	ambiguous	0.255	Stabilizing	0.923	D	0.377	neutral	None	None	None	None	N
E/S	0.1899	likely_benign	0.2194	benign	-0.924	Destabilizing	0.633	D	0.361	neutral	None	None	None	None	N
E/T	0.1877	likely_benign	0.21	benign	-0.659	Destabilizing	0.775	D	0.381	neutral	None	None	None	None	N
E/V	0.1522	likely_benign	0.1795	benign	-0.118	Destabilizing	0.949	D	0.433	neutral	D	0.525930672	None	None	N
E/W	0.8485	likely_pathogenic	0.8984	pathogenic	0.215	Stabilizing	0.996	D	0.629	neutral	None	None	None	None	N
E/Y	0.4942	ambiguous	0.5669	pathogenic	0.183	Stabilizing	0.923	D	0.511	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.