TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7185	21778;21779;21780	chr2:178723547;178723546;178723545	chr2:179588274;179588273;179588272
N2AB	6868	20827;20828;20829	chr2:178723547;178723546;178723545	chr2:179588274;179588273;179588272
N2A	5941	18046;18047;18048	chr2:178723547;178723546;178723545	chr2:179588274;179588273;179588272
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-56
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1417
• 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
I/F	rs552242411	-1.512	0.934	N	0.555	0.46	0.627026710118	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/F	rs552242411	-1.512	0.934	N	0.555	0.46	0.627026710118	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/F	rs552242411	-1.512	0.934	N	0.555	0.46	0.627026710118	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/F	rs552242411	-1.512	0.934	N	0.555	0.46	0.627026710118	gnomAD-4.0.0	1.82672E-05	None	None	None	None	N	None	1.74319E-05	0	None	0	0	None	0	0	2.04842E-05	0	0
I/L	None	None	0.267	N	0.269	0.221	0.495238560318	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
I/L	None	None	0.267	N	0.269	0.221	0.495238560318	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	0	None	0	1.93125E-04	None	0	0	0	0	0
I/T	rs771134456	-2.431	0.801	D	0.458	0.395	0.720981639776	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs771134456	-2.431	0.801	D	0.458	0.395	0.720981639776	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs771134456	-2.431	0.801	D	0.458	0.395	0.720981639776	gnomAD-4.0.0	5.12686E-06	None	None	None	None	N	None	6.76819E-05	0	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
I/A	0.5036	ambiguous	0.4793	ambiguous	-2.214	Highly Destabilizing	0.029	N	0.233	neutral	None	None	None	None	N
I/C	0.7526	likely_pathogenic	0.7545	pathogenic	-1.098	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
I/D	0.8226	likely_pathogenic	0.8071	pathogenic	-2.077	Highly Destabilizing	0.974	D	0.646	neutral	None	None	None	None	N
I/E	0.7426	likely_pathogenic	0.7155	pathogenic	-1.975	Destabilizing	0.974	D	0.629	neutral	None	None	None	None	N
I/F	0.1851	likely_benign	0.1912	benign	-1.442	Destabilizing	0.934	D	0.555	neutral	N	0.486697196	None	None	N
I/G	0.7628	likely_pathogenic	0.748	pathogenic	-2.643	Highly Destabilizing	0.728	D	0.561	neutral	None	None	None	None	N
I/H	0.6267	likely_pathogenic	0.6125	pathogenic	-2.001	Highly Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
I/K	0.5594	ambiguous	0.5444	ambiguous	-1.579	Destabilizing	0.842	D	0.625	neutral	None	None	None	None	N
I/L	0.1377	likely_benign	0.14	benign	-1.032	Destabilizing	0.267	N	0.269	neutral	N	0.486226215	None	None	N
I/M	0.1205	likely_benign	0.1259	benign	-0.664	Destabilizing	0.267	N	0.277	neutral	N	0.498027048	None	None	N
I/N	0.4174	ambiguous	0.3913	ambiguous	-1.501	Destabilizing	0.989	D	0.649	neutral	D	0.537846863	None	None	N
I/P	0.8781	likely_pathogenic	0.8784	pathogenic	-1.402	Destabilizing	0.974	D	0.65	neutral	None	None	None	None	N
I/Q	0.617	likely_pathogenic	0.6101	pathogenic	-1.567	Destabilizing	0.974	D	0.651	neutral	None	None	None	None	N
I/R	0.4176	ambiguous	0.4074	ambiguous	-1.08	Destabilizing	0.974	D	0.648	neutral	None	None	None	None	N
I/S	0.4214	ambiguous	0.3999	ambiguous	-2.126	Highly Destabilizing	0.669	D	0.509	neutral	N	0.497586202	None	None	N
I/T	0.353	ambiguous	0.3324	benign	-1.906	Destabilizing	0.801	D	0.458	neutral	D	0.530675387	None	None	N
I/V	0.091	likely_benign	0.0889	benign	-1.402	Destabilizing	0.005	N	0.111	neutral	N	0.47527789	None	None	N
I/W	0.7938	likely_pathogenic	0.8019	pathogenic	-1.715	Destabilizing	0.998	D	0.656	neutral	None	None	None	None	N
I/Y	0.5058	ambiguous	0.4929	ambiguous	-1.466	Destabilizing	0.991	D	0.613	neutral	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.