TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20342	61249;61250;61251	chr2:178590701;178590700;178590699	chr2:179455428;179455427;179455426
N2AB	18701	56326;56327;56328	chr2:178590701;178590700;178590699	chr2:179455428;179455427;179455426
N2A	17774	53545;53546;53547	chr2:178590701;178590700;178590699	chr2:179455428;179455427;179455426
N2B	11277	34054;34055;34056	chr2:178590701;178590700;178590699	chr2:179455428;179455427;179455426
Novex-1	11402	34429;34430;34431	chr2:178590701;178590700;178590699	chr2:179455428;179455427;179455426
Novex-2	11469	34630;34631;34632	chr2:178590701;178590700;178590699	chr2:179455428;179455427;179455426
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: Fn3-35
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1573
• 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	rs1015533049	None	0.999	N	0.601	0.387	0.390060412749	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1015533049	None	0.999	N	0.601	0.387	0.390060412749	gnomAD-4.0.0	1.23993E-06	None	None	None	None	N	None	1.33551E-05	0	None	0	0	None	0	0	8.47877E-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	0.449	ambiguous	0.4728	ambiguous	-1.414	Destabilizing	0.999	D	0.677	prob.neutral	N	0.492007935	None	None	N
E/C	0.9145	likely_pathogenic	0.9196	pathogenic	-0.663	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/D	0.6815	likely_pathogenic	0.7533	pathogenic	-1.468	Destabilizing	0.999	D	0.555	neutral	N	0.499516353	None	None	N
E/F	0.948	likely_pathogenic	0.9481	pathogenic	-0.993	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/G	0.7071	likely_pathogenic	0.7193	pathogenic	-1.84	Destabilizing	1.0	D	0.711	prob.delet.	N	0.515899088	None	None	N
E/H	0.8513	likely_pathogenic	0.8597	pathogenic	-0.988	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.6024	likely_pathogenic	0.6077	pathogenic	-0.198	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/K	0.6371	likely_pathogenic	0.587	pathogenic	-1.136	Destabilizing	0.999	D	0.601	neutral	N	0.520367101	None	None	N
E/L	0.7309	likely_pathogenic	0.7431	pathogenic	-0.198	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/M	0.6779	likely_pathogenic	0.692	pathogenic	0.525	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.8155	likely_pathogenic	0.8496	pathogenic	-1.462	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/P	0.9976	likely_pathogenic	0.9979	pathogenic	-0.587	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/Q	0.2214	likely_benign	0.2388	benign	-1.205	Destabilizing	1.0	D	0.665	neutral	N	0.505725722	None	None	N
E/R	0.7356	likely_pathogenic	0.6938	pathogenic	-0.973	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/S	0.5477	ambiguous	0.5864	pathogenic	-2.13	Highly Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
E/T	0.5827	likely_pathogenic	0.603	pathogenic	-1.727	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/V	0.4368	ambiguous	0.4516	ambiguous	-0.587	Destabilizing	1.0	D	0.712	prob.delet.	N	0.472889722	None	None	N
E/W	0.9886	likely_pathogenic	0.9875	pathogenic	-0.919	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/Y	0.9311	likely_pathogenic	0.9262	pathogenic	-0.728	Destabilizing	1.0	D	0.763	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.