TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4004	12235;12236;12237	chr2:178741223;178741222;178741221	chr2:179605950;179605949;179605948
N2AB	3687	11284;11285;11286	chr2:178741223;178741222;178741221	chr2:179605950;179605949;179605948
N2A	None	None	chr2:None	chr2:None
N2B	3641	11146;11147;11148	chr2:178741223;178741222;178741221	chr2:179605950;179605949;179605948
Novex-1	3766	11521;11522;11523	chr2:178741223;178741222;178741221	chr2:179605950;179605949;179605948
Novex-2	3833	11722;11723;11724	chr2:178741223;178741222;178741221	chr2:179605950;179605949;179605948
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-28
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.6864
• 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	rs376000381	-0.475	None	N	0.153	0.06	None	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	3.72393E-04	0	None	0	0	None	0	None	0	0	0
E/G	rs376000381	-0.475	None	N	0.153	0.06	None	gnomAD-3.1.2	1.18309E-04	None	None	None	None	I	None	4.34405E-04	0	0	0	0	None	0	0	0	0	0
E/G	rs376000381	-0.475	None	N	0.153	0.06	None	gnomAD-4.0.0	1.7975E-05	None	None	None	None	I	None	3.87121E-04	0	None	0	0	None	0	0	0	0	0
E/K	rs755242569	0.662	0.001	N	0.188	0.061	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs755242569	0.662	0.001	N	0.188	0.061	None	gnomAD-4.0.0	1.09501E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4391E-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	0.1335	likely_benign	0.1163	benign	-0.289	Destabilizing	0.042	N	0.342	neutral	N	0.444961429	None	None	I
E/C	0.8017	likely_pathogenic	0.7378	pathogenic	-0.037	Destabilizing	0.958	D	0.302	neutral	None	None	None	None	I
E/D	0.1576	likely_benign	0.1269	benign	-0.274	Destabilizing	0.001	N	0.178	neutral	N	0.449466837	None	None	I
E/F	0.7061	likely_pathogenic	0.6308	pathogenic	-0.236	Destabilizing	0.859	D	0.306	neutral	None	None	None	None	I
E/G	0.1091	likely_benign	0.0988	benign	-0.453	Destabilizing	None	N	0.153	neutral	N	0.446828127	None	None	I
E/H	0.4617	ambiguous	0.3918	ambiguous	0.124	Stabilizing	0.497	N	0.356	neutral	None	None	None	None	I
E/I	0.3504	ambiguous	0.3018	benign	0.1	Stabilizing	0.667	D	0.327	neutral	None	None	None	None	I
E/K	0.0878	likely_benign	0.09	benign	0.393	Stabilizing	0.001	N	0.188	neutral	N	0.448526661	None	None	I
E/L	0.3741	ambiguous	0.3151	benign	0.1	Stabilizing	0.22	N	0.378	neutral	None	None	None	None	I
E/M	0.3938	ambiguous	0.3354	benign	0.132	Stabilizing	0.883	D	0.297	neutral	None	None	None	None	I
E/N	0.2359	likely_benign	0.1948	benign	0.093	Stabilizing	0.124	N	0.247	neutral	None	None	None	None	I
E/P	0.5103	ambiguous	0.4661	ambiguous	-0.01	Destabilizing	0.667	D	0.363	neutral	None	None	None	None	I
E/Q	0.1423	likely_benign	0.1264	benign	0.123	Stabilizing	0.001	N	0.217	neutral	N	0.461344658	None	None	I
E/R	0.1782	likely_benign	0.1703	benign	0.589	Stabilizing	0.001	N	0.227	neutral	None	None	None	None	I
E/S	0.1997	likely_benign	0.1582	benign	-0.054	Destabilizing	0.055	N	0.241	neutral	None	None	None	None	I
E/T	0.2126	likely_benign	0.175	benign	0.085	Stabilizing	0.22	N	0.331	neutral	None	None	None	None	I
E/V	0.2148	likely_benign	0.1843	benign	-0.01	Destabilizing	0.175	N	0.345	neutral	D	0.553599986	None	None	I
E/W	0.8115	likely_pathogenic	0.7501	pathogenic	-0.119	Destabilizing	0.958	D	0.339	neutral	None	None	None	None	I
E/Y	0.5824	likely_pathogenic	0.5155	ambiguous	-0.001	Destabilizing	0.667	D	0.315	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.