TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7715	23368;23369;23370	chr2:178720619;178720618;178720617	chr2:179585346;179585345;179585344
N2AB	7398	22417;22418;22419	chr2:178720619;178720618;178720617	chr2:179585346;179585345;179585344
N2A	6471	19636;19637;19638	chr2:178720619;178720618;178720617	chr2:179585346;179585345;179585344
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-62
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.6233
• 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
K/E	None	None	0.003	N	0.267	0.052	0.132336055621	gnomAD-4.0.0	1.59966E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86779E-06	0	0
K/T	None	None	0.173	N	0.533	0.188	0.231231049324	gnomAD-4.0.0	1.60001E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.04062E-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
K/A	0.6273	likely_pathogenic	0.7533	pathogenic	-0.473	Destabilizing	0.317	N	0.54	neutral	None	None	None	None	I
K/C	0.8954	likely_pathogenic	0.9385	pathogenic	-0.576	Destabilizing	0.987	D	0.69	prob.neutral	None	None	None	None	I
K/D	0.8747	likely_pathogenic	0.9233	pathogenic	0.299	Stabilizing	0.317	N	0.545	neutral	None	None	None	None	I
K/E	0.4277	ambiguous	0.5798	pathogenic	0.386	Stabilizing	0.003	N	0.267	neutral	N	0.404120641	None	None	I
K/F	0.9183	likely_pathogenic	0.9545	pathogenic	-0.411	Destabilizing	0.889	D	0.604	neutral	None	None	None	None	I
K/G	0.7826	likely_pathogenic	0.8707	pathogenic	-0.764	Destabilizing	0.481	N	0.556	neutral	None	None	None	None	I
K/H	0.5002	ambiguous	0.6014	pathogenic	-0.954	Destabilizing	0.574	D	0.491	neutral	None	None	None	None	I
K/I	0.6168	likely_pathogenic	0.7314	pathogenic	0.25	Stabilizing	0.128	N	0.597	neutral	N	0.45345617	None	None	I
K/L	0.5875	likely_pathogenic	0.7137	pathogenic	0.25	Stabilizing	0.027	N	0.526	neutral	None	None	None	None	I
K/M	0.5037	ambiguous	0.6394	pathogenic	-0.013	Destabilizing	0.748	D	0.493	neutral	None	None	None	None	I
K/N	0.7772	likely_pathogenic	0.8599	pathogenic	-0.192	Destabilizing	0.021	N	0.31	neutral	N	0.470985212	None	None	I
K/P	0.6879	likely_pathogenic	0.7504	pathogenic	0.038	Stabilizing	0.868	D	0.507	neutral	None	None	None	None	I
K/Q	0.2293	likely_benign	0.322	benign	-0.231	Destabilizing	0.001	N	0.3	neutral	N	0.498863173	None	None	I
K/R	0.0866	likely_benign	0.0981	benign	-0.251	Destabilizing	0.061	N	0.498	neutral	N	0.456669834	None	None	I
K/S	0.7545	likely_pathogenic	0.8494	pathogenic	-0.854	Destabilizing	0.317	N	0.485	neutral	None	None	None	None	I
K/T	0.4957	ambiguous	0.6295	pathogenic	-0.567	Destabilizing	0.173	N	0.533	neutral	N	0.50471171	None	None	I
K/V	0.6015	likely_pathogenic	0.716	pathogenic	0.038	Stabilizing	0.112	N	0.517	neutral	None	None	None	None	I
K/W	0.8641	likely_pathogenic	0.916	pathogenic	-0.328	Destabilizing	0.991	D	0.712	prob.delet.	None	None	None	None	I
K/Y	0.8241	likely_pathogenic	0.8893	pathogenic	-0.018	Destabilizing	0.235	N	0.573	neutral	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.