TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19885	59878;59879;59880	chr2:178592251;178592250;178592249	chr2:179456978;179456977;179456976
N2AB	18244	54955;54956;54957	chr2:178592251;178592250;178592249	chr2:179456978;179456977;179456976
N2A	17317	52174;52175;52176	chr2:178592251;178592250;178592249	chr2:179456978;179456977;179456976
N2B	10820	32683;32684;32685	chr2:178592251;178592250;178592249	chr2:179456978;179456977;179456976
Novex-1	10945	33058;33059;33060	chr2:178592251;178592250;178592249	chr2:179456978;179456977;179456976
Novex-2	11012	33259;33260;33261	chr2:178592251;178592250;178592249	chr2:179456978;179456977;179456976
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: Fn3-32
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4911
• 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/K	rs777362856	0.57	0.002	N	0.152	0.137	0.191931220699	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.6E-05	None	4.68E-05	0	0
E/K	rs777362856	0.57	0.002	N	0.152	0.137	0.191931220699	gnomAD-4.0.0	5.4811E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73792E-04	0	8.14143E-05	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	0.1061	likely_benign	0.1081	benign	-0.445	Destabilizing	0.139	N	0.315	neutral	N	0.446061343	None	None	N
E/C	0.6043	likely_pathogenic	0.6133	pathogenic	0.042	Stabilizing	0.995	D	0.458	neutral	None	None	None	None	N
E/D	0.1622	likely_benign	0.1728	benign	-0.465	Destabilizing	0.425	N	0.273	neutral	N	0.45835585	None	None	N
E/F	0.5305	ambiguous	0.5401	ambiguous	-0.288	Destabilizing	0.893	D	0.545	neutral	None	None	None	None	N
E/G	0.1957	likely_benign	0.2038	benign	-0.676	Destabilizing	0.425	N	0.363	neutral	N	0.484022298	None	None	N
E/H	0.2534	likely_benign	0.2741	benign	-0.222	Destabilizing	0.944	D	0.421	neutral	None	None	None	None	N
E/I	0.1653	likely_benign	0.1604	benign	0.141	Stabilizing	0.543	D	0.403	neutral	None	None	None	None	N
E/K	0.1027	likely_benign	0.114	benign	0.369	Stabilizing	0.002	N	0.152	neutral	N	0.409060393	None	None	N
E/L	0.206	likely_benign	0.2084	benign	0.141	Stabilizing	0.003	N	0.381	neutral	None	None	None	None	N
E/M	0.2608	likely_benign	0.2575	benign	0.341	Stabilizing	0.893	D	0.499	neutral	None	None	None	None	N
E/N	0.2076	likely_benign	0.2116	benign	-0.034	Destabilizing	0.704	D	0.278	neutral	None	None	None	None	N
E/P	0.913	likely_pathogenic	0.9296	pathogenic	-0.034	Destabilizing	0.828	D	0.489	neutral	None	None	None	None	N
E/Q	0.084	likely_benign	0.0896	benign	0.018	Stabilizing	0.01	N	0.135	neutral	N	0.425453997	None	None	N
E/R	0.1547	likely_benign	0.1805	benign	0.512	Stabilizing	0.003	N	0.147	neutral	None	None	None	None	N
E/S	0.1562	likely_benign	0.1621	benign	-0.188	Destabilizing	0.495	N	0.274	neutral	None	None	None	None	N
E/T	0.1198	likely_benign	0.118	benign	0.006	Stabilizing	0.495	N	0.32	neutral	None	None	None	None	N
E/V	0.1035	likely_benign	0.1025	benign	-0.034	Destabilizing	0.002	N	0.319	neutral	N	0.433228119	None	None	N
E/W	0.7742	likely_pathogenic	0.7983	pathogenic	-0.111	Destabilizing	0.995	D	0.476	neutral	None	None	None	None	N
E/Y	0.4435	ambiguous	0.4532	ambiguous	-0.027	Destabilizing	0.944	D	0.58	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.