TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25363	76312;76313;76314	chr2:178570045;178570044;178570043	chr2:179434772;179434771;179434770
N2AB	23722	71389;71390;71391	chr2:178570045;178570044;178570043	chr2:179434772;179434771;179434770
N2A	22795	68608;68609;68610	chr2:178570045;178570044;178570043	chr2:179434772;179434771;179434770
N2B	16298	49117;49118;49119	chr2:178570045;178570044;178570043	chr2:179434772;179434771;179434770
Novex-1	16423	49492;49493;49494	chr2:178570045;178570044;178570043	chr2:179434772;179434771;179434770
Novex-2	16490	49693;49694;49695	chr2:178570045;178570044;178570043	chr2:179434772;179434771;179434770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-72
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.6364
• Predicted PPI site: I

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
R/C	rs757511354	-0.664	1.0	N	0.706	0.43	0.684613241775	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	6.54E-05	None	0	0	0
R/C	rs757511354	-0.664	1.0	N	0.706	0.43	0.684613241775	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.42E-05	0	0	0	1.94099E-04	None	0	0	0	0	0
R/C	rs757511354	-0.664	1.0	N	0.706	0.43	0.684613241775	gnomAD-4.0.0	2.85157E-05	None	None	None	None	I	None	2.67251E-05	0	None	0	2.45711E-04	None	0	1.64636E-04	2.28894E-05	3.29453E-05	3.20287E-05
R/H	rs749274818	-1.065	1.0	N	0.671	0.355	0.293147016451	gnomAD-2.1.1	2.51E-05	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	3.27E-05	None	0	3.14E-05	0
R/H	rs749274818	-1.065	1.0	N	0.671	0.355	0.293147016451	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	4.83E-05	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs749274818	-1.065	1.0	N	0.671	0.355	0.293147016451	gnomAD-4.0.0	2.54158E-05	None	None	None	None	I	None	5.34259E-05	1.668E-05	None	0	0	None	0	0	2.79766E-05	2.1964E-05	1.60149E-05
R/L	None	None	0.913	N	0.599	0.364	0.644876160298	gnomAD-4.0.0	6.84396E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99617E-07	0	0
R/S	None	None	0.913	N	0.589	0.273	0.38342384377	gnomAD-4.0.0	1.36879E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7992E-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
R/A	0.9364	likely_pathogenic	0.8911	pathogenic	-0.288	Destabilizing	0.845	D	0.579	neutral	None	None	None	None	I
R/C	0.5396	ambiguous	0.3724	ambiguous	-0.609	Destabilizing	1.0	D	0.706	prob.neutral	N	0.483778728	None	None	I
R/D	0.9794	likely_pathogenic	0.9655	pathogenic	-0.07	Destabilizing	0.975	D	0.659	neutral	None	None	None	None	I
R/E	0.8969	likely_pathogenic	0.8386	pathogenic	0.068	Stabilizing	0.916	D	0.594	neutral	None	None	None	None	I
R/F	0.935	likely_pathogenic	0.8783	pathogenic	-0.159	Destabilizing	0.987	D	0.705	prob.neutral	None	None	None	None	I
R/G	0.8729	likely_pathogenic	0.7946	pathogenic	-0.565	Destabilizing	0.954	D	0.603	neutral	N	0.481194607	None	None	I
R/H	0.3173	likely_benign	0.2106	benign	-0.845	Destabilizing	1.0	D	0.671	neutral	N	0.483003578	None	None	I
R/I	0.8777	likely_pathogenic	0.8013	pathogenic	0.442	Stabilizing	0.975	D	0.711	prob.delet.	None	None	None	None	I
R/K	0.4119	ambiguous	0.3545	ambiguous	-0.273	Destabilizing	0.818	D	0.547	neutral	None	None	None	None	I
R/L	0.8181	likely_pathogenic	0.708	pathogenic	0.442	Stabilizing	0.913	D	0.599	neutral	N	0.484993269	None	None	I
R/M	0.8847	likely_pathogenic	0.7955	pathogenic	-0.254	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
R/N	0.9443	likely_pathogenic	0.9055	pathogenic	-0.286	Destabilizing	0.975	D	0.637	neutral	None	None	None	None	I
R/P	0.9854	likely_pathogenic	0.9755	pathogenic	0.22	Stabilizing	0.993	D	0.718	prob.delet.	N	0.48473978	None	None	I
R/Q	0.3721	ambiguous	0.2447	benign	-0.255	Destabilizing	0.987	D	0.661	neutral	None	None	None	None	I
R/S	0.9231	likely_pathogenic	0.8676	pathogenic	-0.767	Destabilizing	0.913	D	0.589	neutral	N	0.482171285	None	None	I
R/T	0.8383	likely_pathogenic	0.7513	pathogenic	-0.45	Destabilizing	0.033	N	0.461	neutral	None	None	None	None	I
R/V	0.89	likely_pathogenic	0.8246	pathogenic	0.22	Stabilizing	0.95	D	0.633	neutral	None	None	None	None	I
R/W	0.5988	likely_pathogenic	0.4196	ambiguous	-0.06	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
R/Y	0.8183	likely_pathogenic	0.6852	pathogenic	0.281	Stabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	I

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.