TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17480	52663;52664;52665	chr2:178608445;178608444;178608443	chr2:179473172;179473171;179473170
N2AB	15839	47740;47741;47742	chr2:178608445;178608444;178608443	chr2:179473172;179473171;179473170
N2A	14912	44959;44960;44961	chr2:178608445;178608444;178608443	chr2:179473172;179473171;179473170
N2B	8415	25468;25469;25470	chr2:178608445;178608444;178608443	chr2:179473172;179473171;179473170
Novex-1	8540	25843;25844;25845	chr2:178608445;178608444;178608443	chr2:179473172;179473171;179473170
Novex-2	8607	26044;26045;26046	chr2:178608445;178608444;178608443	chr2:179473172;179473171;179473170
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: Fn3-15
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5452
• 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/Q	rs2055452595	None	0.684	N	0.409	0.103	0.21737058555	gnomAD-4.0.0	8.25532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.08341E-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	0.2057	likely_benign	0.1815	benign	-0.563	Destabilizing	0.684	D	0.335	neutral	N	0.463551026	None	None	N
E/C	0.8188	likely_pathogenic	0.7808	pathogenic	-0.388	Destabilizing	0.996	D	0.447	neutral	None	None	None	None	N
E/D	0.1764	likely_benign	0.1659	benign	-0.753	Destabilizing	0.003	N	0.095	neutral	N	0.45799049	None	None	N
E/F	0.7989	likely_pathogenic	0.7618	pathogenic	-0.02	Destabilizing	0.984	D	0.411	neutral	None	None	None	None	N
E/G	0.2268	likely_benign	0.1925	benign	-0.871	Destabilizing	0.684	D	0.372	neutral	N	0.458222564	None	None	N
E/H	0.5014	ambiguous	0.4634	ambiguous	0.006	Stabilizing	0.953	D	0.383	neutral	None	None	None	None	N
E/I	0.405	ambiguous	0.3814	ambiguous	0.253	Stabilizing	0.953	D	0.427	neutral	None	None	None	None	N
E/K	0.209	likely_benign	0.1822	benign	-0.224	Destabilizing	0.012	N	0.088	neutral	N	0.427224866	None	None	N
E/L	0.4372	ambiguous	0.3973	ambiguous	0.253	Stabilizing	0.854	D	0.41	neutral	None	None	None	None	N
E/M	0.4752	ambiguous	0.4451	ambiguous	0.378	Stabilizing	0.996	D	0.385	neutral	None	None	None	None	N
E/N	0.341	ambiguous	0.306	benign	-0.728	Destabilizing	0.037	N	0.206	neutral	None	None	None	None	N
E/P	0.9425	likely_pathogenic	0.9323	pathogenic	0.003	Stabilizing	0.953	D	0.375	neutral	None	None	None	None	N
E/Q	0.1733	likely_benign	0.1557	benign	-0.614	Destabilizing	0.684	D	0.409	neutral	N	0.460665436	None	None	N
E/R	0.3316	likely_benign	0.2943	benign	0.139	Stabilizing	0.59	D	0.364	neutral	None	None	None	None	N
E/S	0.2184	likely_benign	0.1949	benign	-0.938	Destabilizing	0.543	D	0.353	neutral	None	None	None	None	N
E/T	0.1893	likely_benign	0.1715	benign	-0.684	Destabilizing	0.742	D	0.325	neutral	None	None	None	None	N
E/V	0.234	likely_benign	0.212	benign	0.003	Stabilizing	0.815	D	0.391	neutral	N	0.414084998	None	None	N
E/W	0.8925	likely_pathogenic	0.8772	pathogenic	0.229	Stabilizing	0.996	D	0.547	neutral	None	None	None	None	N
E/Y	0.679	likely_pathogenic	0.6281	pathogenic	0.231	Stabilizing	0.984	D	0.403	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.