TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32171	96736;96737;96738	chr2:178543462;178543461;178543460	chr2:179408189;179408188;179408187
N2AB	30530	91813;91814;91815	chr2:178543462;178543461;178543460	chr2:179408189;179408188;179408187
N2A	29603	89032;89033;89034	chr2:178543462;178543461;178543460	chr2:179408189;179408188;179408187
N2B	23106	69541;69542;69543	chr2:178543462;178543461;178543460	chr2:179408189;179408188;179408187
Novex-1	23231	69916;69917;69918	chr2:178543462;178543461;178543460	chr2:179408189;179408188;179408187
Novex-2	23298	70117;70118;70119	chr2:178543462;178543461;178543460	chr2:179408189;179408188;179408187
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: Fn3-122
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.4581
• 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	rs778618339	0.048	0.984	N	0.607	0.326	0.345175991111	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs778618339	0.048	0.984	N	0.607	0.326	0.345175991111	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85829E-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	0.2637	likely_benign	0.3024	benign	-0.476	Destabilizing	0.985	D	0.615	neutral	N	0.469100606	None	None	N
E/C	0.9442	likely_pathogenic	0.9527	pathogenic	-0.043	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/D	0.6204	likely_pathogenic	0.6383	pathogenic	-0.372	Destabilizing	0.945	D	0.545	neutral	N	0.492070387	None	None	N
E/F	0.9733	likely_pathogenic	0.9771	pathogenic	-0.287	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/G	0.5275	ambiguous	0.548	ambiguous	-0.683	Destabilizing	0.999	D	0.665	neutral	N	0.483107165	None	None	N
E/H	0.891	likely_pathogenic	0.905	pathogenic	-0.087	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
E/I	0.7529	likely_pathogenic	0.776	pathogenic	0.039	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.5276	ambiguous	0.5393	ambiguous	0.415	Stabilizing	0.984	D	0.607	neutral	N	0.467191729	None	None	N
E/L	0.8302	likely_pathogenic	0.8546	pathogenic	0.039	Stabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	N
E/M	0.8097	likely_pathogenic	0.8299	pathogenic	0.173	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/N	0.7709	likely_pathogenic	0.7784	pathogenic	-0.021	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.5233	ambiguous	0.5471	ambiguous	-0.113	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
E/Q	0.2916	likely_benign	0.3134	benign	0.017	Stabilizing	0.887	D	0.307	neutral	D	0.522348613	None	None	N
E/R	0.6578	likely_pathogenic	0.6753	pathogenic	0.59	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
E/S	0.5089	ambiguous	0.5429	ambiguous	-0.163	Destabilizing	0.989	D	0.662	neutral	None	None	None	None	N
E/T	0.5714	likely_pathogenic	0.632	pathogenic	0.014	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
E/V	0.5408	ambiguous	0.5875	pathogenic	-0.113	Destabilizing	0.997	D	0.69	prob.neutral	N	0.473966132	None	None	N
E/W	0.9934	likely_pathogenic	0.9938	pathogenic	-0.088	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Y	0.9581	likely_pathogenic	0.9662	pathogenic	-0.024	Destabilizing	1.0	D	0.704	prob.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.