TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5195	15808;15809;15810	chr2:178733806;178733805;178733804	chr2:179598533;179598532;179598531
N2AB	4878	14857;14858;14859	chr2:178733806;178733805;178733804	chr2:179598533;179598532;179598531
N2A	3951	12076;12077;12078	chr2:178733806;178733805;178733804	chr2:179598533;179598532;179598531
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-35
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.866
• Predicted PPI site: I

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	rs72648931	-0.117	0.454	N	0.415	0.244	None	gnomAD-2.1.1	9.81729E-04	None	None	None	None	I	None	1.08696E-02	3.39443E-04	None	0	0	None	0	None	0	0	0
E/G	rs72648931	-0.117	0.454	N	0.415	0.244	None	gnomAD-3.1.2	2.82582E-03	None	None	None	None	I	None	9.91413E-03	1.04781E-03	0	0	0	None	0	0	0	0	1.43678E-03
E/G	rs72648931	-0.117	0.454	N	0.415	0.244	None	1000 genomes	2.39617E-03	None	None	None	None	I	None	9.1E-03	0	None	None	0	0	None	None	None	0	None
E/G	rs72648931	-0.117	0.454	N	0.415	0.244	None	gnomAD-4.0.0	4.85801E-04	None	None	None	None	I	None	9.52724E-03	4.99917E-04	None	0	0	None	0	0	1.18669E-05	0	4.00154E-04

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	0.097	likely_benign	0.1126	benign	0.005	Stabilizing	0.005	N	0.213	neutral	N	0.498671488	None	None	I
E/C	0.7395	likely_pathogenic	0.816	pathogenic	-0.219	Destabilizing	0.993	D	0.442	neutral	None	None	None	None	I
E/D	0.0922	likely_benign	0.1137	benign	-0.369	Destabilizing	0.625	D	0.439	neutral	N	0.504786338	None	None	I
E/F	0.5381	ambiguous	0.6435	pathogenic	0.009	Stabilizing	0.974	D	0.463	neutral	None	None	None	None	I
E/G	0.1188	likely_benign	0.141	benign	-0.118	Destabilizing	0.454	N	0.415	neutral	N	0.509040832	None	None	I
E/H	0.3136	likely_benign	0.3825	ambiguous	0.633	Stabilizing	0.991	D	0.387	neutral	None	None	None	None	I
E/I	0.2492	likely_benign	0.3249	benign	0.274	Stabilizing	0.949	D	0.495	neutral	None	None	None	None	I
E/K	0.0942	likely_benign	0.0991	benign	0.457	Stabilizing	0.801	D	0.421	neutral	N	0.510101189	None	None	I
E/L	0.2304	likely_benign	0.2862	benign	0.274	Stabilizing	0.842	D	0.522	neutral	None	None	None	None	I
E/M	0.3161	likely_benign	0.3841	ambiguous	0.009	Stabilizing	0.998	D	0.425	neutral	None	None	None	None	I
E/N	0.1677	likely_benign	0.2187	benign	0.122	Stabilizing	0.842	D	0.457	neutral	None	None	None	None	I
E/P	0.2442	likely_benign	0.2844	benign	0.202	Stabilizing	0.974	D	0.471	neutral	None	None	None	None	I
E/Q	0.0986	likely_benign	0.1073	benign	0.144	Stabilizing	0.891	D	0.488	neutral	N	0.470630369	None	None	I
E/R	0.1751	likely_benign	0.1859	benign	0.709	Stabilizing	0.974	D	0.425	neutral	None	None	None	None	I
E/S	0.1183	likely_benign	0.1452	benign	0.013	Stabilizing	0.172	N	0.218	neutral	None	None	None	None	I
E/T	0.1584	likely_benign	0.1983	benign	0.125	Stabilizing	0.728	D	0.421	neutral	None	None	None	None	I
E/V	0.1517	likely_benign	0.1831	benign	0.202	Stabilizing	0.669	D	0.49	neutral	D	0.572310485	None	None	I
E/W	0.7844	likely_pathogenic	0.8486	pathogenic	0.065	Stabilizing	0.998	D	0.529	neutral	None	None	None	None	I
E/Y	0.4054	ambiguous	0.497	ambiguous	0.238	Stabilizing	0.991	D	0.441	neutral	None	None	None	None	I

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.