TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2849	8770;8771;8772	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881
N2AB	2849	8770;8771;8772	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881
N2A	2849	8770;8771;8772	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881
N2B	2803	8632;8633;8634	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881
Novex-1	2803	8632;8633;8634	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881
Novex-2	2803	8632;8633;8634	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881
Novex-3	2849	8770;8771;8772	chr2:178770156;178770155;178770154	chr2:179634883;179634882;179634881

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-18
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1248
• 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
H/N	None	None	0.999	D	0.613	0.456	0.213573922156	gnomAD-4.0.0	1.59046E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85647E-06	0	0
H/Q	rs2091263013	None	1.0	N	0.754	0.269	0.199424873507	gnomAD-4.0.0	1.59045E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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
H/A	0.9687	likely_pathogenic	0.973	pathogenic	-1.669	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
H/C	0.6468	likely_pathogenic	0.7172	pathogenic	-1.099	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
H/D	0.9825	likely_pathogenic	0.9815	pathogenic	-1.443	Destabilizing	1.0	D	0.773	deleterious	D	0.604786688	None	None	N
H/E	0.9776	likely_pathogenic	0.977	pathogenic	-1.274	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
H/F	0.8783	likely_pathogenic	0.8961	pathogenic	0.041	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
H/G	0.9782	likely_pathogenic	0.9782	pathogenic	-2.07	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
H/I	0.9651	likely_pathogenic	0.9736	pathogenic	-0.501	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
H/K	0.9391	likely_pathogenic	0.9293	pathogenic	-1.298	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
H/L	0.7976	likely_pathogenic	0.8159	pathogenic	-0.501	Destabilizing	1.0	D	0.831	deleterious	D	0.533653281	None	None	N
H/M	0.9671	likely_pathogenic	0.9706	pathogenic	-0.789	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
H/N	0.7487	likely_pathogenic	0.7814	pathogenic	-1.69	Destabilizing	0.999	D	0.613	neutral	D	0.5249805	None	None	N
H/P	0.9935	likely_pathogenic	0.9907	pathogenic	-0.878	Destabilizing	1.0	D	0.855	deleterious	D	0.565354002	None	None	N
H/Q	0.8084	likely_pathogenic	0.8189	pathogenic	-1.298	Destabilizing	1.0	D	0.754	deleterious	N	0.460167236	None	None	N
H/R	0.681	likely_pathogenic	0.6629	pathogenic	-1.54	Destabilizing	1.0	D	0.721	prob.delet.	N	0.4493112	None	None	N
H/S	0.907	likely_pathogenic	0.9281	pathogenic	-1.872	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
H/T	0.9677	likely_pathogenic	0.9735	pathogenic	-1.59	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
H/V	0.9401	likely_pathogenic	0.9545	pathogenic	-0.878	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
H/W	0.856	likely_pathogenic	0.8635	pathogenic	0.495	Stabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
H/Y	0.5038	ambiguous	0.5647	pathogenic	0.414	Stabilizing	0.999	D	0.637	neutral	N	0.430235186	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.