TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7305	22138;22139;22140	chr2:178723094;178723093;178723092	chr2:179587821;179587820;179587819
N2AB	6988	21187;21188;21189	chr2:178723094;178723093;178723092	chr2:179587821;179587820;179587819
N2A	6061	18406;18407;18408	chr2:178723094;178723093;178723092	chr2:179587821;179587820;179587819
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-57
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.3836
• 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	rs1553911785	None	0.042	N	0.402	0.209	0.332902724076	gnomAD-4.0.0	6.36687E-06	None	None	None	None	I	None	0	0	None	0	1.10951E-04	None	0	0	0	0	0
E/D	rs763316110	-0.955	0.175	D	0.285	0.061	0.218112801441	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs763316110	-0.955	0.175	D	0.285	0.061	0.218112801441	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs763316110	-0.955	0.175	D	0.285	0.061	0.218112801441	gnomAD-4.0.0	6.40681E-06	None	None	None	None	I	None	8.45823E-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	0.1217	likely_benign	0.115	benign	-0.706	Destabilizing	0.042	N	0.402	neutral	N	0.491328324	None	None	I
E/C	0.6851	likely_pathogenic	0.7139	pathogenic	-0.156	Destabilizing	0.883	D	0.527	neutral	None	None	None	None	I
E/D	0.2003	likely_benign	0.2559	benign	-0.854	Destabilizing	0.175	N	0.285	neutral	D	0.531886108	None	None	I
E/F	0.535	ambiguous	0.5494	ambiguous	-0.699	Destabilizing	0.497	N	0.556	neutral	None	None	None	None	I
E/G	0.1556	likely_benign	0.1581	benign	-0.981	Destabilizing	0.175	N	0.475	neutral	N	0.486519385	None	None	I
E/H	0.2915	likely_benign	0.2996	benign	-0.952	Destabilizing	0.859	D	0.483	neutral	None	None	None	None	I
E/I	0.2393	likely_benign	0.2408	benign	0.013	Stabilizing	0.004	N	0.34	neutral	None	None	None	None	I
E/K	0.0987	likely_benign	0.096	benign	-0.115	Destabilizing	0.175	N	0.273	neutral	N	0.496405311	None	None	I
E/L	0.292	likely_benign	0.2924	benign	0.013	Stabilizing	None	N	0.315	neutral	None	None	None	None	I
E/M	0.315	likely_benign	0.3021	benign	0.458	Stabilizing	0.497	N	0.517	neutral	None	None	None	None	I
E/N	0.2455	likely_benign	0.2934	benign	-0.425	Destabilizing	0.22	N	0.403	neutral	None	None	None	None	I
E/P	0.9576	likely_pathogenic	0.9658	pathogenic	-0.206	Destabilizing	0.667	D	0.488	neutral	None	None	None	None	I
E/Q	0.0877	likely_benign	0.0835	benign	-0.387	Destabilizing	0.301	N	0.427	neutral	D	0.529480521	None	None	I
E/R	0.1457	likely_benign	0.1364	benign	-0.071	Destabilizing	0.667	D	0.425	neutral	None	None	None	None	I
E/S	0.1444	likely_benign	0.1475	benign	-0.68	Destabilizing	0.005	N	0.101	neutral	None	None	None	None	I
E/T	0.1418	likely_benign	0.1398	benign	-0.452	Destabilizing	0.055	N	0.389	neutral	None	None	None	None	I
E/V	0.1577	likely_benign	0.156	benign	-0.206	Destabilizing	0.001	N	0.283	neutral	D	0.534406338	None	None	I
E/W	0.733	likely_pathogenic	0.7378	pathogenic	-0.573	Destabilizing	0.958	D	0.569	neutral	None	None	None	None	I
E/Y	0.4746	ambiguous	0.4933	ambiguous	-0.453	Destabilizing	0.667	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.