TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5642	17149;17150;17151	chr2:178731951;178731950;178731949	chr2:179596678;179596677;179596676
N2AB	5325	16198;16199;16200	chr2:178731951;178731950;178731949	chr2:179596678;179596677;179596676
N2A	4398	13417;13418;13419	chr2:178731951;178731950;178731949	chr2:179596678;179596677;179596676
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-40
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5593
• 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/D	rs2080608666	None	0.165	D	0.311	0.07	0.263612267334	gnomAD-4.0.0	6.86864E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02997E-07	0	0
E/K	rs1448901680	0.247	0.001	N	0.159	0.184	0.270447802918	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	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	0.0822	likely_benign	0.09	benign	-0.544	Destabilizing	0.003	N	0.145	neutral	N	0.509142534	None	None	I
E/C	0.6368	likely_pathogenic	0.7118	pathogenic	-0.364	Destabilizing	0.981	D	0.315	neutral	None	None	None	None	I
E/D	0.1312	likely_benign	0.1344	benign	-0.664	Destabilizing	0.165	N	0.311	neutral	D	0.53479034	None	None	I
E/F	0.5661	likely_pathogenic	0.6196	pathogenic	0.311	Stabilizing	0.932	D	0.345	neutral	None	None	None	None	I
E/G	0.1083	likely_benign	0.1263	benign	-0.894	Destabilizing	0.324	N	0.395	neutral	D	0.524189345	None	None	I
E/H	0.324	likely_benign	0.3755	ambiguous	0.414	Stabilizing	0.818	D	0.343	neutral	None	None	None	None	I
E/I	0.2029	likely_benign	0.2415	benign	0.406	Stabilizing	0.69	D	0.366	neutral	None	None	None	None	I
E/K	0.0992	likely_benign	0.1195	benign	0.003	Stabilizing	0.001	N	0.159	neutral	N	0.469237352	None	None	I
E/L	0.2284	likely_benign	0.2713	benign	0.406	Stabilizing	0.388	N	0.431	neutral	None	None	None	None	I
E/M	0.257	likely_benign	0.3054	benign	0.526	Stabilizing	0.932	D	0.317	neutral	None	None	None	None	I
E/N	0.1787	likely_benign	0.1997	benign	-0.731	Destabilizing	0.388	N	0.33	neutral	None	None	None	None	I
E/P	0.217	likely_benign	0.2205	benign	0.11	Stabilizing	0.001	N	0.138	neutral	None	None	None	None	I
E/Q	0.0968	likely_benign	0.1109	benign	-0.571	Destabilizing	0.193	N	0.351	neutral	N	0.496482668	None	None	I
E/R	0.1681	likely_benign	0.1991	benign	0.409	Stabilizing	0.241	N	0.333	neutral	None	None	None	None	I
E/S	0.1355	likely_benign	0.1498	benign	-0.979	Destabilizing	0.116	N	0.289	neutral	None	None	None	None	I
E/T	0.1224	likely_benign	0.1382	benign	-0.663	Destabilizing	0.008	N	0.166	neutral	None	None	None	None	I
E/V	0.1195	likely_benign	0.138	benign	0.11	Stabilizing	0.324	N	0.415	neutral	N	0.488305902	None	None	I
E/W	0.7816	likely_pathogenic	0.8277	pathogenic	0.673	Stabilizing	0.981	D	0.353	neutral	None	None	None	None	I
E/Y	0.403	ambiguous	0.4647	ambiguous	0.624	Stabilizing	0.932	D	0.343	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.