TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8763	26512;26513;26514	chr2:178714487;178714486;178714485	chr2:179579214;179579213;179579212
N2AB	8446	25561;25562;25563	chr2:178714487;178714486;178714485	chr2:179579214;179579213;179579212
N2A	7519	22780;22781;22782	chr2:178714487;178714486;178714485	chr2:179579214;179579213;179579212
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-73
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.7787
• 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/A	rs1453342840	0.161	0.567	N	0.478	0.254	0.365120060079	gnomAD-2.1.1	6.37E-05	None	None	None	None	I	None	2.29621E-04	0	None	0	0	None	0	None	0	0	0
E/A	rs1453342840	0.161	0.567	N	0.478	0.254	0.365120060079	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/A	rs1453342840	0.161	0.567	N	0.478	0.254	0.365120060079	gnomAD-4.0.0	1.97174E-05	None	None	None	None	I	None	7.23903E-05	0	None	0	0	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
E/A	0.0931	likely_benign	0.0983	benign	-0.269	Destabilizing	0.567	D	0.478	neutral	N	0.468432062	None	None	I
E/C	0.7413	likely_pathogenic	0.7826	pathogenic	-0.331	Destabilizing	0.993	D	0.643	neutral	None	None	None	None	I
E/D	0.1173	likely_benign	0.128	benign	-0.381	Destabilizing	0.145	N	0.533	neutral	N	0.50229392	None	None	I
E/F	0.5166	ambiguous	0.577	pathogenic	-0.104	Destabilizing	0.996	D	0.579	neutral	None	None	None	None	I
E/G	0.0976	likely_benign	0.1124	benign	-0.444	Destabilizing	0.813	D	0.451	neutral	N	0.512470841	None	None	I
E/H	0.2821	likely_benign	0.3138	benign	0.438	Stabilizing	0.942	D	0.487	neutral	None	None	None	None	I
E/I	0.2394	likely_benign	0.269	benign	0.154	Stabilizing	0.915	D	0.582	neutral	None	None	None	None	I
E/K	0.0728	likely_benign	0.0831	benign	0.216	Stabilizing	0.549	D	0.545	neutral	N	0.501773845	None	None	I
E/L	0.2052	likely_benign	0.2316	benign	0.154	Stabilizing	0.841	D	0.506	neutral	None	None	None	None	I
E/M	0.2869	likely_benign	0.3207	benign	-0.02	Destabilizing	0.879	D	0.517	neutral	None	None	None	None	I
E/N	0.1759	likely_benign	0.2003	benign	-0.15	Destabilizing	0.71	D	0.507	neutral	None	None	None	None	I
E/P	0.2185	likely_benign	0.2159	benign	0.032	Stabilizing	0.002	N	0.297	neutral	None	None	None	None	I
E/Q	0.0815	likely_benign	0.0836	benign	-0.109	Destabilizing	0.023	N	0.188	neutral	N	0.423275776	None	None	I
E/R	0.1302	likely_benign	0.148	benign	0.575	Stabilizing	0.85	D	0.514	neutral	None	None	None	None	I
E/S	0.1151	likely_benign	0.1265	benign	-0.303	Destabilizing	0.634	D	0.517	neutral	None	None	None	None	I
E/T	0.1461	likely_benign	0.1677	benign	-0.154	Destabilizing	0.894	D	0.433	neutral	None	None	None	None	I
E/V	0.1445	likely_benign	0.1596	benign	0.032	Stabilizing	0.852	D	0.443	neutral	N	0.499330494	None	None	I
E/W	0.7149	likely_pathogenic	0.7715	pathogenic	0.035	Stabilizing	0.999	D	0.654	neutral	None	None	None	None	I
E/Y	0.3801	ambiguous	0.4377	ambiguous	0.135	Stabilizing	0.995	D	0.526	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.