TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17947	54064;54065;54066	chr2:178605456;178605455;178605454	chr2:179470183;179470182;179470181
N2AB	16306	49141;49142;49143	chr2:178605456;178605455;178605454	chr2:179470183;179470182;179470181
N2A	15379	46360;46361;46362	chr2:178605456;178605455;178605454	chr2:179470183;179470182;179470181
N2B	8882	26869;26870;26871	chr2:178605456;178605455;178605454	chr2:179470183;179470182;179470181
Novex-1	9007	27244;27245;27246	chr2:178605456;178605455;178605454	chr2:179470183;179470182;179470181
Novex-2	9074	27445;27446;27447	chr2:178605456;178605455;178605454	chr2:179470183;179470182;179470181
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: Fn3-18
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.8334
• 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/K	rs1445321949	0.848	0.928	N	0.649	0.277	0.264547087235	gnomAD-2.1.1	8.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
E/K	rs1445321949	0.848	0.928	N	0.649	0.277	0.264547087235	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1445321949	0.848	0.928	N	0.649	0.277	0.264547087235	gnomAD-4.0.0	1.98681E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.63147E-05	0	1.60457E-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	0.2206	likely_benign	0.1891	benign	-0.351	Destabilizing	0.928	D	0.663	neutral	N	0.509534032	None	None	I
E/C	0.8947	likely_pathogenic	0.8771	pathogenic	0.091	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
E/D	0.0969	likely_benign	0.0918	benign	-0.294	Destabilizing	0.039	N	0.275	neutral	N	0.497028881	None	None	I
E/F	0.8095	likely_pathogenic	0.7603	pathogenic	-0.345	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
E/G	0.3162	likely_benign	0.2616	benign	-0.519	Destabilizing	0.978	D	0.676	prob.neutral	N	0.478926428	None	None	I
E/H	0.6095	likely_pathogenic	0.5511	ambiguous	-0.115	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
E/I	0.4011	ambiguous	0.368	ambiguous	0.05	Stabilizing	0.992	D	0.733	prob.delet.	None	None	None	None	I
E/K	0.2759	likely_benign	0.2219	benign	0.45	Stabilizing	0.928	D	0.649	neutral	N	0.514825208	None	None	I
E/L	0.4367	ambiguous	0.3838	ambiguous	0.05	Stabilizing	0.992	D	0.729	prob.delet.	None	None	None	None	I
E/M	0.5488	ambiguous	0.4969	ambiguous	0.209	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
E/N	0.3112	likely_benign	0.2687	benign	0.169	Stabilizing	0.968	D	0.743	deleterious	None	None	None	None	I
E/P	0.4795	ambiguous	0.4172	ambiguous	-0.064	Destabilizing	0.992	D	0.745	deleterious	None	None	None	None	I
E/Q	0.2133	likely_benign	0.188	benign	0.19	Stabilizing	0.978	D	0.73	prob.delet.	N	0.512670337	None	None	I
E/R	0.4445	ambiguous	0.3758	ambiguous	0.568	Stabilizing	0.992	D	0.762	deleterious	None	None	None	None	I
E/S	0.2714	likely_benign	0.2327	benign	0.026	Stabilizing	0.944	D	0.67	neutral	None	None	None	None	I
E/T	0.3113	likely_benign	0.2778	benign	0.168	Stabilizing	0.983	D	0.707	prob.neutral	None	None	None	None	I
E/V	0.2684	likely_benign	0.2427	benign	-0.064	Destabilizing	0.989	D	0.742	deleterious	N	0.474864731	None	None	I
E/W	0.9419	likely_pathogenic	0.9252	pathogenic	-0.225	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	I
E/Y	0.6943	likely_pathogenic	0.627	pathogenic	-0.104	Destabilizing	0.999	D	0.726	prob.delet.	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.