TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26573	79942;79943;79944	chr2:178566415;178566414;178566413	chr2:179431142;179431141;179431140
N2AB	24932	75019;75020;75021	chr2:178566415;178566414;178566413	chr2:179431142;179431141;179431140
N2A	24005	72238;72239;72240	chr2:178566415;178566414;178566413	chr2:179431142;179431141;179431140
N2B	17508	52747;52748;52749	chr2:178566415;178566414;178566413	chr2:179431142;179431141;179431140
Novex-1	17633	53122;53123;53124	chr2:178566415;178566414;178566413	chr2:179431142;179431141;179431140
Novex-2	17700	53323;53324;53325	chr2:178566415;178566414;178566413	chr2:179431142;179431141;179431140
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: Fn3-81
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6305
• 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/G	None	None	0.988	N	0.743	0.515	0.524741657026	gnomAD-4.0.0	6.84334E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99533E-07	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	0.376	ambiguous	0.3442	ambiguous	-0.32	Destabilizing	0.958	D	0.736	prob.delet.	N	0.467747934	None	None	I
E/C	0.9447	likely_pathogenic	0.9407	pathogenic	0.094	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
E/D	0.148	likely_benign	0.1477	benign	-0.293	Destabilizing	0.067	N	0.283	neutral	N	0.514267848	None	None	I
E/F	0.9149	likely_pathogenic	0.9116	pathogenic	-0.31	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
E/G	0.4789	ambiguous	0.4423	ambiguous	-0.497	Destabilizing	0.988	D	0.743	deleterious	N	0.509045325	None	None	I
E/H	0.7736	likely_pathogenic	0.7831	pathogenic	-0.082	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
E/I	0.6389	likely_pathogenic	0.6156	pathogenic	0.104	Stabilizing	0.995	D	0.776	deleterious	None	None	None	None	I
E/K	0.3767	ambiguous	0.3605	ambiguous	0.442	Stabilizing	0.958	D	0.673	neutral	N	0.514825208	None	None	I
E/L	0.6855	likely_pathogenic	0.6712	pathogenic	0.104	Stabilizing	0.995	D	0.769	deleterious	None	None	None	None	I
E/M	0.722	likely_pathogenic	0.705	pathogenic	0.234	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/N	0.4704	ambiguous	0.4552	ambiguous	0.19	Stabilizing	0.982	D	0.755	deleterious	None	None	None	None	I
E/P	0.7063	likely_pathogenic	0.6848	pathogenic	-0.017	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	I
E/Q	0.3317	likely_benign	0.3199	benign	0.2	Stabilizing	0.994	D	0.732	prob.delet.	N	0.472445195	None	None	I
E/R	0.5787	likely_pathogenic	0.5854	pathogenic	0.585	Stabilizing	0.995	D	0.746	deleterious	None	None	None	None	I
E/S	0.4656	ambiguous	0.4431	ambiguous	0.026	Stabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	I
E/T	0.5122	ambiguous	0.4836	ambiguous	0.169	Stabilizing	0.991	D	0.762	deleterious	None	None	None	None	I
E/V	0.4421	ambiguous	0.4142	ambiguous	-0.017	Destabilizing	0.994	D	0.782	deleterious	N	0.494450244	None	None	I
E/W	0.9737	likely_pathogenic	0.9752	pathogenic	-0.192	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
E/Y	0.8433	likely_pathogenic	0.8412	pathogenic	-0.066	Destabilizing	1.0	D	0.771	deleterious	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.