TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2908	8947;8948;8949	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584
N2AB	2908	8947;8948;8949	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584
N2A	2908	8947;8948;8949	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584
N2B	2862	8809;8810;8811	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584
Novex-1	2862	8809;8810;8811	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584
Novex-2	2862	8809;8810;8811	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584
Novex-3	2908	8947;8948;8949	chr2:178769859;178769858;178769857	chr2:179634586;179634585;179634584

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-19
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.431
• 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
F/L	None	None	0.948	N	0.597	0.416	0.40017627803	gnomAD-4.0.0	1.59049E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85651E-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
F/A	0.9249	likely_pathogenic	0.8504	pathogenic	-0.979	Destabilizing	0.992	D	0.64	neutral	None	None	None	None	N
F/C	0.8246	likely_pathogenic	0.7231	pathogenic	-0.341	Destabilizing	1.0	D	0.678	prob.neutral	N	0.50967633	None	None	N
F/D	0.946	likely_pathogenic	0.9125	pathogenic	0.655	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
F/E	0.9479	likely_pathogenic	0.9211	pathogenic	0.633	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
F/G	0.9643	likely_pathogenic	0.9368	pathogenic	-1.17	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
F/H	0.8569	likely_pathogenic	0.8064	pathogenic	0.25	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
F/I	0.7468	likely_pathogenic	0.6148	pathogenic	-0.493	Destabilizing	0.978	D	0.623	neutral	N	0.499072437	None	None	N
F/K	0.9609	likely_pathogenic	0.9428	pathogenic	-0.14	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
F/L	0.9759	likely_pathogenic	0.9552	pathogenic	-0.493	Destabilizing	0.948	D	0.597	neutral	N	0.47113012	None	None	N
F/M	0.8986	likely_pathogenic	0.8359	pathogenic	-0.427	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
F/N	0.8966	likely_pathogenic	0.8448	pathogenic	-0.11	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
F/P	0.9788	likely_pathogenic	0.9639	pathogenic	-0.637	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
F/Q	0.9292	likely_pathogenic	0.8984	pathogenic	-0.171	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
F/R	0.913	likely_pathogenic	0.8809	pathogenic	0.336	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
F/S	0.8599	likely_pathogenic	0.7582	pathogenic	-0.772	Destabilizing	0.998	D	0.635	neutral	N	0.429483707	None	None	N
F/T	0.914	likely_pathogenic	0.8423	pathogenic	-0.703	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
F/V	0.7108	likely_pathogenic	0.5656	pathogenic	-0.637	Destabilizing	0.543	D	0.42	neutral	N	0.464033452	None	None	N
F/W	0.8047	likely_pathogenic	0.7727	pathogenic	-0.292	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
F/Y	0.2939	likely_benign	0.2596	benign	-0.289	Destabilizing	0.998	D	0.595	neutral	N	0.482006266	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.