TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26895	80908;80909;80910	chr2:178565449;178565448;178565447	chr2:179430176;179430175;179430174
N2AB	25254	75985;75986;75987	chr2:178565449;178565448;178565447	chr2:179430176;179430175;179430174
N2A	24327	73204;73205;73206	chr2:178565449;178565448;178565447	chr2:179430176;179430175;179430174
N2B	17830	53713;53714;53715	chr2:178565449;178565448;178565447	chr2:179430176;179430175;179430174
Novex-1	17955	54088;54089;54090	chr2:178565449;178565448;178565447	chr2:179430176;179430175;179430174
Novex-2	18022	54289;54290;54291	chr2:178565449;178565448;178565447	chr2:179430176;179430175;179430174
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-139
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3003
• 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/D	None	None	0.981	N	0.421	0.249	0.296679040009	gnomAD-4.0.0	2.05321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69876E-06	0	0
E/K	None	None	0.996	N	0.458	0.294	0.28492961333	gnomAD-4.0.0	3.422E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49797E-06	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	0.1686	likely_benign	0.2028	benign	-0.571	Destabilizing	0.998	D	0.536	neutral	N	0.515528923	None	None	N
E/C	0.7725	likely_pathogenic	0.8385	pathogenic	-0.017	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/D	0.0967	likely_benign	0.1115	benign	-0.486	Destabilizing	0.981	D	0.421	neutral	N	0.446300911	None	None	N
E/F	0.7347	likely_pathogenic	0.8091	pathogenic	-0.519	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/G	0.1521	likely_benign	0.1856	benign	-0.785	Destabilizing	0.996	D	0.571	neutral	N	0.495903013	None	None	N
E/H	0.3809	ambiguous	0.4737	ambiguous	-0.482	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
E/I	0.4226	ambiguous	0.5201	ambiguous	-0.033	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/K	0.1161	likely_benign	0.159	benign	0.166	Stabilizing	0.996	D	0.458	neutral	N	0.488803682	None	None	N
E/L	0.4369	ambiguous	0.5286	ambiguous	-0.033	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/M	0.4222	ambiguous	0.4909	ambiguous	0.246	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/N	0.1767	likely_benign	0.2213	benign	-0.111	Destabilizing	0.91	D	0.325	neutral	None	None	None	None	N
E/P	0.8998	likely_pathogenic	0.9262	pathogenic	-0.192	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
E/Q	0.1257	likely_benign	0.1481	benign	-0.089	Destabilizing	0.999	D	0.607	neutral	N	0.453266956	None	None	N
E/R	0.2219	likely_benign	0.2954	benign	0.305	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/S	0.1572	likely_benign	0.1884	benign	-0.291	Destabilizing	0.997	D	0.477	neutral	None	None	None	None	N
E/T	0.2007	likely_benign	0.2458	benign	-0.12	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
E/V	0.2594	likely_benign	0.318	benign	-0.192	Destabilizing	1.0	D	0.711	prob.delet.	N	0.479613401	None	None	N
E/W	0.8874	likely_pathogenic	0.9285	pathogenic	-0.366	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Y	0.5739	likely_pathogenic	0.6808	pathogenic	-0.279	Destabilizing	1.0	D	0.733	prob.delet.	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.