TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21621	65086;65087;65088	chr2:178584780;178584779;178584778	chr2:179449507;179449506;179449505
N2AB	19980	60163;60164;60165	chr2:178584780;178584779;178584778	chr2:179449507;179449506;179449505
N2A	19053	57382;57383;57384	chr2:178584780;178584779;178584778	chr2:179449507;179449506;179449505
N2B	12556	37891;37892;37893	chr2:178584780;178584779;178584778	chr2:179449507;179449506;179449505
Novex-1	12681	38266;38267;38268	chr2:178584780;178584779;178584778	chr2:179449507;179449506;179449505
Novex-2	12748	38467;38468;38469	chr2:178584780;178584779;178584778	chr2:179449507;179449506;179449505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-44
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1916
• 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
V/A	None	None	0.052	N	0.68	0.366	0.470318359215	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	0
V/F	None	None	0.317	N	0.833	0.293	0.391000631824	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
V/A	0.4749	ambiguous	0.4907	ambiguous	-1.9	Destabilizing	0.052	N	0.68	prob.neutral	N	0.481290875	None	None	N
V/C	0.9052	likely_pathogenic	0.8915	pathogenic	-1.546	Destabilizing	0.935	D	0.793	deleterious	None	None	None	None	N
V/D	0.9859	likely_pathogenic	0.9857	pathogenic	-1.792	Destabilizing	0.484	N	0.853	deleterious	N	0.505155575	None	None	N
V/E	0.9577	likely_pathogenic	0.9568	pathogenic	-1.635	Destabilizing	0.555	D	0.821	deleterious	None	None	None	None	N
V/F	0.4932	ambiguous	0.4595	ambiguous	-1.173	Destabilizing	0.317	N	0.833	deleterious	N	0.504253294	None	None	N
V/G	0.8194	likely_pathogenic	0.8154	pathogenic	-2.385	Highly Destabilizing	0.484	N	0.828	deleterious	D	0.552493354	None	None	N
V/H	0.9823	likely_pathogenic	0.9812	pathogenic	-1.88	Destabilizing	0.935	D	0.839	deleterious	None	None	None	None	N
V/I	0.0727	likely_benign	0.0686	benign	-0.591	Destabilizing	None	N	0.254	neutral	N	0.49329793	None	None	N
V/K	0.9716	likely_pathogenic	0.9711	pathogenic	-1.629	Destabilizing	0.555	D	0.828	deleterious	None	None	None	None	N
V/L	0.2718	likely_benign	0.2512	benign	-0.591	Destabilizing	None	N	0.343	neutral	N	0.520268313	None	None	N
V/M	0.3167	likely_benign	0.3025	benign	-0.632	Destabilizing	0.007	N	0.502	neutral	None	None	None	None	N
V/N	0.9549	likely_pathogenic	0.9521	pathogenic	-1.748	Destabilizing	0.791	D	0.853	deleterious	None	None	None	None	N
V/P	0.9268	likely_pathogenic	0.9255	pathogenic	-0.996	Destabilizing	0.791	D	0.837	deleterious	None	None	None	None	N
V/Q	0.9517	likely_pathogenic	0.9522	pathogenic	-1.67	Destabilizing	0.555	D	0.836	deleterious	None	None	None	None	N
V/R	0.9517	likely_pathogenic	0.9533	pathogenic	-1.354	Destabilizing	0.555	D	0.849	deleterious	None	None	None	None	N
V/S	0.8338	likely_pathogenic	0.841	pathogenic	-2.428	Highly Destabilizing	0.262	N	0.818	deleterious	None	None	None	None	N
V/T	0.5785	likely_pathogenic	0.6042	pathogenic	-2.115	Highly Destabilizing	0.149	N	0.712	prob.delet.	None	None	None	None	N
V/W	0.972	likely_pathogenic	0.9704	pathogenic	-1.48	Destabilizing	0.935	D	0.831	deleterious	None	None	None	None	N
V/Y	0.928	likely_pathogenic	0.9163	pathogenic	-1.142	Destabilizing	0.555	D	0.817	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.