TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25092	75499;75500;75501	chr2:178570858;178570857;178570856	chr2:179435585;179435584;179435583
N2AB	23451	70576;70577;70578	chr2:178570858;178570857;178570856	chr2:179435585;179435584;179435583
N2A	22524	67795;67796;67797	chr2:178570858;178570857;178570856	chr2:179435585;179435584;179435583
N2B	16027	48304;48305;48306	chr2:178570858;178570857;178570856	chr2:179435585;179435584;179435583
Novex-1	16152	48679;48680;48681	chr2:178570858;178570857;178570856	chr2:179435585;179435584;179435583
Novex-2	16219	48880;48881;48882	chr2:178570858;178570857;178570856	chr2:179435585;179435584;179435583
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: Fn3-70
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6718
• Predicted PPI site: N

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/K	rs397517700	0.332	0.016	N	0.162	0.159	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	1.65317E-04	0	None	0	0	None	0	None	0	0	1.4041E-04
E/K	rs397517700	0.332	0.016	N	0.162	0.159	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs397517700	0.332	0.016	N	0.162	0.159	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs397517700	0.332	0.016	N	0.162	0.159	None	gnomAD-4.0.0	6.81722E-06	None	None	None	None	N	None	1.19987E-04	0	None	0	0	None	0	0	0	0	3.20184E-05

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	0.099	likely_benign	0.1049	benign	-0.453	Destabilizing	0.334	N	0.483	neutral	N	0.518153515	None	None	N
E/C	0.6971	likely_pathogenic	0.7158	pathogenic	-0.125	Destabilizing	0.992	D	0.554	neutral	None	None	None	None	N
E/D	0.1088	likely_benign	0.1131	benign	-0.38	Destabilizing	0.004	N	0.148	neutral	N	0.471170431	None	None	N
E/F	0.5601	ambiguous	0.5845	pathogenic	-0.24	Destabilizing	0.92	D	0.543	neutral	None	None	None	None	N
E/G	0.1278	likely_benign	0.1383	benign	-0.663	Destabilizing	0.549	D	0.564	neutral	N	0.492586912	None	None	N
E/H	0.3367	likely_benign	0.3422	ambiguous	0.023	Stabilizing	0.92	D	0.557	neutral	None	None	None	None	N
E/I	0.1995	likely_benign	0.2125	benign	0.07	Stabilizing	0.739	D	0.595	neutral	None	None	None	None	N
E/K	0.0849	likely_benign	0.089	benign	0.263	Stabilizing	0.016	N	0.162	neutral	N	0.498663677	None	None	N
E/L	0.1907	likely_benign	0.2013	benign	0.07	Stabilizing	0.447	N	0.577	neutral	None	None	None	None	N
E/M	0.2655	likely_benign	0.2826	benign	0.162	Stabilizing	0.92	D	0.551	neutral	None	None	None	None	N
E/N	0.1718	likely_benign	0.1802	benign	-0.131	Destabilizing	0.447	N	0.567	neutral	None	None	None	None	N
E/P	0.2579	likely_benign	0.2656	benign	-0.084	Destabilizing	0.92	D	0.607	neutral	None	None	None	None	N
E/Q	0.099	likely_benign	0.1019	benign	-0.078	Destabilizing	0.016	N	0.119	neutral	N	0.467836839	None	None	N
E/R	0.1614	likely_benign	0.1648	benign	0.513	Stabilizing	0.447	N	0.565	neutral	None	None	None	None	N
E/S	0.1386	likely_benign	0.145	benign	-0.288	Destabilizing	0.617	D	0.46	neutral	None	None	None	None	N
E/T	0.1633	likely_benign	0.1736	benign	-0.111	Destabilizing	0.617	D	0.547	neutral	None	None	None	None	N
E/V	0.1229	likely_benign	0.1303	benign	-0.084	Destabilizing	0.016	N	0.384	neutral	N	0.509496746	None	None	N
E/W	0.8295	likely_pathogenic	0.8381	pathogenic	-0.05	Destabilizing	0.992	D	0.611	neutral	None	None	None	None	N
E/Y	0.4423	ambiguous	0.4544	ambiguous	0.012	Stabilizing	0.972	D	0.549	neutral	None	None	None	None	N

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.