TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9629	29110;29111;29112	chr2:178707682;178707681;178707680	chr2:179572409;179572408;179572407
N2AB	9312	28159;28160;28161	chr2:178707682;178707681;178707680	chr2:179572409;179572408;179572407
N2A	8385	25378;25379;25380	chr2:178707682;178707681;178707680	chr2:179572409;179572408;179572407
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-82
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4115
• 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	None	None	0.998	None	0.578	0.384	0.440077040801	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4331	ambiguous	0.2842	benign	-0.503	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
E/C	0.9851	likely_pathogenic	0.9707	pathogenic	-0.368	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
E/D	0.2832	likely_benign	0.2379	benign	-0.616	Destabilizing	0.434	N	0.259	neutral	None	None	None	None	N
E/F	0.9505	likely_pathogenic	0.9016	pathogenic	-0.041	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/G	0.5456	ambiguous	0.3551	ambiguous	-0.774	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/H	0.9013	likely_pathogenic	0.8	pathogenic	0.137	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.6829	likely_pathogenic	0.552	ambiguous	0.205	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/K	0.5819	likely_pathogenic	0.3936	ambiguous	-0.022	Destabilizing	0.998	D	0.578	neutral	None	None	None	None	N
E/L	0.7175	likely_pathogenic	0.5952	pathogenic	0.205	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/M	0.7654	likely_pathogenic	0.6438	pathogenic	0.218	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/N	0.6242	likely_pathogenic	0.479	ambiguous	-0.545	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
E/P	0.7481	likely_pathogenic	0.6358	pathogenic	-0.01	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/Q	0.4147	ambiguous	0.2894	benign	-0.454	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
E/R	0.7515	likely_pathogenic	0.5933	pathogenic	0.339	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/S	0.5947	likely_pathogenic	0.4394	ambiguous	-0.715	Destabilizing	0.997	D	0.614	neutral	None	None	None	None	N
E/T	0.6042	likely_pathogenic	0.4393	ambiguous	-0.49	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/V	0.4763	ambiguous	0.3458	ambiguous	-0.01	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/W	0.9881	likely_pathogenic	0.9716	pathogenic	0.198	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/Y	0.9239	likely_pathogenic	0.8563	pathogenic	0.213	Stabilizing	1.0	D	0.739	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.