TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17295	52108;52109;52110	chr2:178609427;178609426;178609425	chr2:179474154;179474153;179474152
N2AB	15654	47185;47186;47187	chr2:178609427;178609426;178609425	chr2:179474154;179474153;179474152
N2A	14727	44404;44405;44406	chr2:178609427;178609426;178609425	chr2:179474154;179474153;179474152
N2B	8230	24913;24914;24915	chr2:178609427;178609426;178609425	chr2:179474154;179474153;179474152
Novex-1	8355	25288;25289;25290	chr2:178609427;178609426;178609425	chr2:179474154;179474153;179474152
Novex-2	8422	25489;25490;25491	chr2:178609427;178609426;178609425	chr2:179474154;179474153;179474152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-112
• Domain position: 45
• Structural Position: 77
• Q(SASA): 0.4051
• 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
K/N	rs72632861	0.328	0.942	D	0.686	0.219	0.32053947749	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/N	rs72632861	0.328	0.942	D	0.686	0.219	0.32053947749	gnomAD-4.0.0	8.21766E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.04275E-03	4.49991E-06	0	1.65898E-05
K/R	None	None	0.032	D	0.406	0.093	0.379020345274	gnomAD-4.0.0	1.36958E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79994E-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
K/A	0.4156	ambiguous	0.3995	ambiguous	-0.069	Destabilizing	0.754	D	0.668	neutral	None	None	None	None	N
K/C	0.8007	likely_pathogenic	0.7968	pathogenic	-0.6	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
K/D	0.5826	likely_pathogenic	0.5668	pathogenic	-0.468	Destabilizing	0.956	D	0.769	deleterious	None	None	None	None	N
K/E	0.2241	likely_benign	0.2139	benign	-0.489	Destabilizing	0.822	D	0.627	neutral	D	0.531957892	None	None	N
K/F	0.8029	likely_pathogenic	0.7958	pathogenic	-0.469	Destabilizing	0.978	D	0.779	deleterious	None	None	None	None	N
K/G	0.4277	ambiguous	0.4162	ambiguous	-0.157	Destabilizing	0.86	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.42	ambiguous	0.4227	ambiguous	-0.203	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
K/I	0.4177	ambiguous	0.4076	ambiguous	0.083	Stabilizing	0.915	D	0.789	deleterious	None	None	None	None	N
K/L	0.4107	ambiguous	0.3999	ambiguous	0.083	Stabilizing	0.754	D	0.721	prob.delet.	None	None	None	None	N
K/M	0.3483	ambiguous	0.3455	ambiguous	-0.313	Destabilizing	0.992	D	0.743	deleterious	D	0.534038192	None	None	N
K/N	0.4452	ambiguous	0.4315	ambiguous	-0.15	Destabilizing	0.942	D	0.686	prob.neutral	D	0.532304609	None	None	N
K/P	0.3871	ambiguous	0.356	ambiguous	0.052	Stabilizing	0.978	D	0.796	deleterious	None	None	None	None	N
K/Q	0.1761	likely_benign	0.1738	benign	-0.275	Destabilizing	0.942	D	0.7	prob.neutral	D	0.532824684	None	None	N
K/R	0.1012	likely_benign	0.0999	benign	-0.236	Destabilizing	0.032	N	0.406	neutral	D	0.532651325	None	None	N
K/S	0.472	ambiguous	0.4598	ambiguous	-0.456	Destabilizing	0.754	D	0.615	neutral	None	None	None	None	N
K/T	0.2607	likely_benign	0.2498	benign	-0.383	Destabilizing	0.032	N	0.439	neutral	D	0.5331714	None	None	N
K/V	0.3886	ambiguous	0.3715	ambiguous	0.052	Stabilizing	0.915	D	0.72	prob.delet.	None	None	None	None	N
K/W	0.8081	likely_pathogenic	0.8109	pathogenic	-0.605	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
K/Y	0.6485	likely_pathogenic	0.6498	pathogenic	-0.272	Destabilizing	0.993	D	0.781	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.