TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5839	17740;17741;17742	chr2:178731150;178731149;178731148	chr2:179595877;179595876;179595875
N2AB	5522	16789;16790;16791	chr2:178731150;178731149;178731148	chr2:179595877;179595876;179595875
N2A	4595	14008;14009;14010	chr2:178731150;178731149;178731148	chr2:179595877;179595876;179595875
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-42
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5029
• 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
P/L	None	None	0.999	N	0.78	0.385	0.536804958393	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	5.66059E-05	0	None	0	0	None	0	0	0	0	0
P/S	None	None	0.998	N	0.736	0.298	0.143124449307	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
P/A	0.1182	likely_benign	0.1515	benign	-0.931	Destabilizing	0.996	D	0.597	neutral	N	0.48941697	None	None	N
P/C	0.6901	likely_pathogenic	0.8445	pathogenic	-0.768	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/D	0.6851	likely_pathogenic	0.829	pathogenic	-0.556	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/E	0.502	ambiguous	0.6921	pathogenic	-0.642	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/F	0.6412	likely_pathogenic	0.7968	pathogenic	-0.977	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/G	0.5432	ambiguous	0.683	pathogenic	-1.134	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
P/H	0.3598	ambiguous	0.5532	ambiguous	-0.613	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/I	0.4049	ambiguous	0.5595	ambiguous	-0.523	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
P/K	0.5881	likely_pathogenic	0.7902	pathogenic	-0.658	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/L	0.177	likely_benign	0.2984	benign	-0.523	Destabilizing	0.999	D	0.78	deleterious	N	0.504309065	None	None	N
P/M	0.4044	ambiguous	0.5517	ambiguous	-0.379	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/N	0.5103	ambiguous	0.6812	pathogenic	-0.378	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/Q	0.3376	likely_benign	0.518	ambiguous	-0.653	Destabilizing	1.0	D	0.836	deleterious	N	0.452489337	None	None	N
P/R	0.3913	ambiguous	0.604	pathogenic	-0.088	Destabilizing	0.999	D	0.837	deleterious	N	0.486550024	None	None	N
P/S	0.2074	likely_benign	0.2965	benign	-0.855	Destabilizing	0.998	D	0.736	prob.delet.	N	0.460688787	None	None	N
P/T	0.1423	likely_benign	0.2061	benign	-0.836	Destabilizing	0.884	D	0.368	neutral	N	0.430693954	None	None	N
P/V	0.2924	likely_benign	0.4121	ambiguous	-0.622	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
P/W	0.8348	likely_pathogenic	0.9207	pathogenic	-1.031	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/Y	0.6524	likely_pathogenic	0.8098	pathogenic	-0.741	Destabilizing	1.0	D	0.837	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.