TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26806	80641;80642;80643	chr2:178565716;178565715;178565714	chr2:179430443;179430442;179430441
N2AB	25165	75718;75719;75720	chr2:178565716;178565715;178565714	chr2:179430443;179430442;179430441
N2A	24238	72937;72938;72939	chr2:178565716;178565715;178565714	chr2:179430443;179430442;179430441
N2B	17741	53446;53447;53448	chr2:178565716;178565715;178565714	chr2:179430443;179430442;179430441
Novex-1	17866	53821;53822;53823	chr2:178565716;178565715;178565714	chr2:179430443;179430442;179430441
Novex-2	17933	54022;54023;54024	chr2:178565716;178565715;178565714	chr2:179430443;179430442;179430441
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-83
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5052
• 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/R	rs181766682	-0.045	0.004	N	0.223	0.139	None	gnomAD-2.1.1	5.36E-05	None	None	None	None	N	None	6.2004E-04	0	None	0	0	None	0	None	0	0	0
H/R	rs181766682	-0.045	0.004	N	0.223	0.139	None	gnomAD-3.1.2	1.57768E-04	None	None	None	None	N	None	5.54912E-04	6.56E-05	0	0	0	None	0	0	0	0	0
H/R	rs181766682	-0.045	0.004	N	0.223	0.139	None	1000 genomes	7.98722E-04	None	None	None	None	N	None	3E-03	0	None	None	0	0	None	None	None	0	None
H/R	rs181766682	-0.045	0.004	N	0.223	0.139	None	gnomAD-4.0.0	3.78027E-05	None	None	None	None	N	None	7.46468E-04	3.33389E-05	None	0	0	None	0	0	8.47711E-07	1.09791E-05	1.60113E-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
H/A	0.6125	likely_pathogenic	0.5956	pathogenic	0.497	Stabilizing	0.682	D	0.381	neutral	None	None	None	None	N
H/C	0.3431	ambiguous	0.3715	ambiguous	0.786	Stabilizing	0.991	D	0.385	neutral	None	None	None	None	N
H/D	0.5154	ambiguous	0.424	ambiguous	0.124	Stabilizing	0.493	N	0.355	neutral	N	0.433665262	None	None	N
H/E	0.6514	likely_pathogenic	0.5936	pathogenic	0.114	Stabilizing	0.64	D	0.319	neutral	None	None	None	None	N
H/F	0.3327	likely_benign	0.3433	ambiguous	0.799	Stabilizing	0.807	D	0.335	neutral	None	None	None	None	N
H/G	0.5873	likely_pathogenic	0.5502	ambiguous	0.279	Stabilizing	0.811	D	0.391	neutral	None	None	None	None	N
H/I	0.5813	likely_pathogenic	0.5329	ambiguous	1.021	Stabilizing	0.924	D	0.406	neutral	None	None	None	None	N
H/K	0.5863	likely_pathogenic	0.5266	ambiguous	0.476	Stabilizing	0.461	N	0.37	neutral	None	None	None	None	N
H/L	0.3427	ambiguous	0.2963	benign	1.021	Stabilizing	0.563	D	0.415	neutral	N	0.515801069	None	None	N
H/M	0.6493	likely_pathogenic	0.6256	pathogenic	0.838	Stabilizing	0.993	D	0.343	neutral	None	None	None	None	N
H/N	0.1962	likely_benign	0.1578	benign	0.545	Stabilizing	0.493	N	0.374	neutral	N	0.464622887	None	None	N
H/P	0.8551	likely_pathogenic	0.8555	pathogenic	0.872	Stabilizing	0.003	N	0.269	neutral	N	0.504720071	None	None	N
H/Q	0.4326	ambiguous	0.3812	ambiguous	0.558	Stabilizing	0.825	D	0.303	neutral	N	0.486344954	None	None	N
H/R	0.3156	likely_benign	0.2747	benign	0.045	Stabilizing	0.004	N	0.223	neutral	N	0.476013317	None	None	N
H/S	0.4269	ambiguous	0.398	ambiguous	0.604	Stabilizing	0.811	D	0.348	neutral	None	None	None	None	N
H/T	0.5046	ambiguous	0.452	ambiguous	0.682	Stabilizing	0.563	D	0.385	neutral	None	None	None	None	N
H/V	0.5227	ambiguous	0.4959	ambiguous	0.872	Stabilizing	0.64	D	0.411	neutral	None	None	None	None	N
H/W	0.474	ambiguous	0.5072	ambiguous	0.664	Stabilizing	0.998	D	0.351	neutral	None	None	None	None	N
H/Y	0.1357	likely_benign	0.1343	benign	1.042	Stabilizing	0.024	N	0.228	neutral	N	0.409020321	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.