TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5415	16468;16469;16470	chr2:178732933;178732932;178732931	chr2:179597660;179597659;179597658
N2AB	5098	15517;15518;15519	chr2:178732933;178732932;178732931	chr2:179597660;179597659;179597658
N2A	4171	12736;12737;12738	chr2:178732933;178732932;178732931	chr2:179597660;179597659;179597658
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-37
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3462
• 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/A	None	None	0.334	N	0.509	0.263	0.285316908763	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05
E/D	None	None	0.004	N	0.271	0.082	0.282575091529	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05
E/K	rs761181567	-0.695	0.007	N	0.292	0.286	0.223847106136	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-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	0.2721	likely_benign	0.2818	benign	-0.986	Destabilizing	0.334	N	0.509	neutral	N	0.518378093	None	None	N
E/C	0.9192	likely_pathogenic	0.9216	pathogenic	-0.578	Destabilizing	0.992	D	0.578	neutral	None	None	None	None	N
E/D	0.1804	likely_benign	0.1765	benign	-1.384	Destabilizing	0.004	N	0.271	neutral	N	0.499581689	None	None	N
E/F	0.8412	likely_pathogenic	0.8503	pathogenic	-0.537	Destabilizing	0.972	D	0.582	neutral	None	None	None	None	N
E/G	0.3599	ambiguous	0.3649	ambiguous	-1.374	Destabilizing	0.549	D	0.547	neutral	N	0.503596455	None	None	N
E/H	0.5332	ambiguous	0.5464	ambiguous	-0.849	Destabilizing	0.92	D	0.527	neutral	None	None	None	None	N
E/I	0.5032	ambiguous	0.5208	ambiguous	0.084	Stabilizing	0.92	D	0.594	neutral	None	None	None	None	N
E/K	0.3611	ambiguous	0.3657	ambiguous	-0.749	Destabilizing	0.007	N	0.292	neutral	N	0.480129136	None	None	N
E/L	0.5497	ambiguous	0.5686	pathogenic	0.084	Stabilizing	0.617	D	0.55	neutral	None	None	None	None	N
E/M	0.5891	likely_pathogenic	0.609	pathogenic	0.597	Stabilizing	0.992	D	0.577	neutral	None	None	None	None	N
E/N	0.3681	ambiguous	0.3738	ambiguous	-1.187	Destabilizing	0.447	N	0.453	neutral	None	None	None	None	N
E/P	0.9824	likely_pathogenic	0.9849	pathogenic	-0.252	Destabilizing	0.92	D	0.579	neutral	None	None	None	None	N
E/Q	0.1834	likely_benign	0.1887	benign	-1.05	Destabilizing	0.045	N	0.375	neutral	N	0.459100503	None	None	N
E/R	0.465	ambiguous	0.4769	ambiguous	-0.562	Destabilizing	0.021	N	0.378	neutral	None	None	None	None	N
E/S	0.305	likely_benign	0.3207	benign	-1.598	Destabilizing	0.447	N	0.491	neutral	None	None	None	None	N
E/T	0.3209	likely_benign	0.3346	benign	-1.261	Destabilizing	0.617	D	0.494	neutral	None	None	None	None	N
E/V	0.3056	likely_benign	0.3167	benign	-0.252	Destabilizing	0.712	D	0.569	neutral	N	0.471971013	None	None	N
E/W	0.9317	likely_pathogenic	0.9327	pathogenic	-0.339	Destabilizing	0.992	D	0.612	neutral	None	None	None	None	N
E/Y	0.7436	likely_pathogenic	0.751	pathogenic	-0.267	Destabilizing	0.972	D	0.591	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.