TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29603	89032;89033;89034	chr2:178554540;178554539;178554538	chr2:179419267;179419266;179419265
N2AB	27962	84109;84110;84111	chr2:178554540;178554539;178554538	chr2:179419267;179419266;179419265
N2A	27035	81328;81329;81330	chr2:178554540;178554539;178554538	chr2:179419267;179419266;179419265
N2B	20538	61837;61838;61839	chr2:178554540;178554539;178554538	chr2:179419267;179419266;179419265
Novex-1	20663	62212;62213;62214	chr2:178554540;178554539;178554538	chr2:179419267;179419266;179419265
Novex-2	20730	62413;62414;62415	chr2:178554540;178554539;178554538	chr2:179419267;179419266;179419265
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: Fn3-103
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.385
• 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	rs777572153	-0.501	0.999	N	0.606	0.387	0.357724736475	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
E/K	rs777572153	-0.501	0.999	N	0.606	0.387	0.357724736475	gnomAD-4.0.0	1.27303E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.14623E-04	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	0.5048	ambiguous	0.5006	ambiguous	-1.128	Destabilizing	0.999	D	0.704	prob.neutral	D	0.523311405	None	None	N
E/C	0.9672	likely_pathogenic	0.9638	pathogenic	-0.475	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/D	0.5394	ambiguous	0.6	pathogenic	-1.002	Destabilizing	0.999	D	0.49	neutral	N	0.468610534	None	None	N
E/F	0.982	likely_pathogenic	0.9842	pathogenic	-0.561	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/G	0.6959	likely_pathogenic	0.6923	pathogenic	-1.497	Destabilizing	1.0	D	0.757	deleterious	N	0.48255096	None	None	N
E/H	0.8751	likely_pathogenic	0.8753	pathogenic	-0.789	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/I	0.7988	likely_pathogenic	0.8074	pathogenic	-0.109	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/K	0.5084	ambiguous	0.5111	ambiguous	-0.494	Destabilizing	0.999	D	0.606	neutral	N	0.513035697	None	None	N
E/L	0.882	likely_pathogenic	0.8895	pathogenic	-0.109	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/M	0.8635	likely_pathogenic	0.8677	pathogenic	0.44	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/N	0.7091	likely_pathogenic	0.7262	pathogenic	-1.006	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/P	0.9612	likely_pathogenic	0.9609	pathogenic	-0.429	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/Q	0.308	likely_benign	0.2894	benign	-0.884	Destabilizing	1.0	D	0.633	neutral	D	0.522617972	None	None	N
E/R	0.6558	likely_pathogenic	0.6575	pathogenic	-0.267	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/S	0.5789	likely_pathogenic	0.5776	pathogenic	-1.382	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
E/T	0.5845	likely_pathogenic	0.5718	pathogenic	-1.059	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/V	0.646	likely_pathogenic	0.65	pathogenic	-0.429	Destabilizing	1.0	D	0.785	deleterious	N	0.472600233	None	None	N
E/W	0.9947	likely_pathogenic	0.9956	pathogenic	-0.232	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/Y	0.9608	likely_pathogenic	0.9656	pathogenic	-0.262	Destabilizing	1.0	D	0.777	deleterious	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.