TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8858	26797;26798;26799	chr2:178714086;178714085;178714084	chr2:179578813;179578812;179578811
N2AB	8541	25846;25847;25848	chr2:178714086;178714085;178714084	chr2:179578813;179578812;179578811
N2A	7614	23065;23066;23067	chr2:178714086;178714085;178714084	chr2:179578813;179578812;179578811
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-74
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7785
• 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	None	None	0.989	D	0.517	0.264	0.393471546983	gnomAD-4.0.0	1.59157E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85858E-06	0	0
E/Q	rs751498825	0.251	0.978	N	0.535	0.255	0.385417323374	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/Q	rs751498825	0.251	0.978	N	0.535	0.255	0.385417323374	gnomAD-4.0.0	1.59163E-06	None	None	None	None	I	None	0	2.28812E-05	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	0.1774	likely_benign	0.1617	benign	-0.105	Destabilizing	0.978	D	0.618	neutral	N	0.502987353	None	None	I
E/C	0.9123	likely_pathogenic	0.8968	pathogenic	-0.189	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
E/D	0.1727	likely_benign	0.1625	benign	-0.25	Destabilizing	0.989	D	0.517	neutral	D	0.527709653	None	None	I
E/F	0.779	likely_pathogenic	0.7418	pathogenic	-0.059	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
E/G	0.2655	likely_benign	0.2476	benign	-0.248	Destabilizing	0.997	D	0.566	neutral	N	0.492622225	None	None	I
E/H	0.547	ambiguous	0.5027	ambiguous	0.484	Stabilizing	1.0	D	0.574	neutral	None	None	None	None	I
E/I	0.3705	ambiguous	0.3359	benign	0.221	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	I
E/K	0.1883	likely_benign	0.1756	benign	0.393	Stabilizing	0.37	N	0.33	neutral	N	0.456060198	None	None	I
E/L	0.4184	ambiguous	0.3934	ambiguous	0.221	Stabilizing	0.998	D	0.625	neutral	None	None	None	None	I
E/M	0.4979	ambiguous	0.4621	ambiguous	0.026	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
E/N	0.3455	ambiguous	0.3232	benign	0.111	Stabilizing	0.998	D	0.597	neutral	None	None	None	None	I
E/P	0.449	ambiguous	0.4271	ambiguous	0.131	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	I
E/Q	0.1597	likely_benign	0.1479	benign	0.136	Stabilizing	0.978	D	0.535	neutral	N	0.501947203	None	None	I
E/R	0.3128	likely_benign	0.2889	benign	0.655	Stabilizing	0.967	D	0.595	neutral	None	None	None	None	I
E/S	0.2505	likely_benign	0.2296	benign	-0.039	Destabilizing	0.983	D	0.611	neutral	None	None	None	None	I
E/T	0.2887	likely_benign	0.2615	benign	0.085	Stabilizing	0.998	D	0.569	neutral	None	None	None	None	I
E/V	0.2292	likely_benign	0.2033	benign	0.131	Stabilizing	0.997	D	0.601	neutral	N	0.510684117	None	None	I
E/W	0.9269	likely_pathogenic	0.9129	pathogenic	0.027	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/Y	0.6468	likely_pathogenic	0.6075	pathogenic	0.173	Stabilizing	0.999	D	0.638	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.