TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5396	16411;16412;16413	chr2:178732990;178732989;178732988	chr2:179597717;179597716;179597715
N2AB	5079	15460;15461;15462	chr2:178732990;178732989;178732988	chr2:179597717;179597716;179597715
N2A	4152	12679;12680;12681	chr2:178732990;178732989;178732988	chr2:179597717;179597716;179597715
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-37
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.5447
• 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	rs780211454	0.582	0.978	N	0.535	0.341	0.338110398507	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs780211454	0.582	0.978	N	0.535	0.341	0.338110398507	gnomAD-4.0.0	1.59178E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.1629	likely_benign	0.1605	benign	-0.642	Destabilizing	0.989	D	0.532	neutral	N	0.474261957	None	None	N
E/C	0.899	likely_pathogenic	0.895	pathogenic	-0.404	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/D	0.2166	likely_benign	0.2253	benign	-0.538	Destabilizing	0.121	N	0.315	neutral	N	0.487671184	None	None	N
E/F	0.8579	likely_pathogenic	0.8662	pathogenic	-0.084	Destabilizing	0.995	D	0.693	prob.neutral	None	None	None	None	N
E/G	0.2631	likely_benign	0.2677	benign	-0.911	Destabilizing	0.978	D	0.524	neutral	N	0.512916345	None	None	N
E/H	0.6057	likely_pathogenic	0.6111	pathogenic	0.215	Stabilizing	1.0	D	0.533	neutral	None	None	None	None	N
E/I	0.392	ambiguous	0.4005	ambiguous	0.065	Stabilizing	0.99	D	0.667	neutral	None	None	None	None	N
E/K	0.1928	likely_benign	0.1852	benign	0.058	Stabilizing	0.978	D	0.535	neutral	N	0.464871682	None	None	N
E/L	0.3969	ambiguous	0.392	ambiguous	0.065	Stabilizing	0.296	N	0.409	neutral	None	None	None	None	N
E/M	0.4678	ambiguous	0.4694	ambiguous	0.117	Stabilizing	0.999	D	0.652	neutral	None	None	None	None	N
E/N	0.369	ambiguous	0.3807	ambiguous	-0.587	Destabilizing	0.995	D	0.512	neutral	None	None	None	None	N
E/P	0.3743	ambiguous	0.354	ambiguous	-0.151	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
E/Q	0.1698	likely_benign	0.1679	benign	-0.49	Destabilizing	0.997	D	0.511	neutral	N	0.479745134	None	None	N
E/R	0.3307	likely_benign	0.3254	benign	0.466	Stabilizing	0.998	D	0.54	neutral	None	None	None	None	N
E/S	0.3483	ambiguous	0.3575	ambiguous	-0.751	Destabilizing	0.983	D	0.507	neutral	None	None	None	None	N
E/T	0.3232	likely_benign	0.3376	benign	-0.517	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
E/V	0.2218	likely_benign	0.225	benign	-0.151	Destabilizing	0.956	D	0.529	neutral	N	0.47953449	None	None	N
E/W	0.9406	likely_pathogenic	0.9445	pathogenic	0.223	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.7391	likely_pathogenic	0.7434	pathogenic	0.194	Stabilizing	0.999	D	0.661	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.