TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29926	90001;90002;90003	chr2:178553124;178553123;178553122	chr2:179417851;179417850;179417849
N2AB	28285	85078;85079;85080	chr2:178553124;178553123;178553122	chr2:179417851;179417850;179417849
N2A	27358	82297;82298;82299	chr2:178553124;178553123;178553122	chr2:179417851;179417850;179417849
N2B	20861	62806;62807;62808	chr2:178553124;178553123;178553122	chr2:179417851;179417850;179417849
Novex-1	20986	63181;63182;63183	chr2:178553124;178553123;178553122	chr2:179417851;179417850;179417849
Novex-2	21053	63382;63383;63384	chr2:178553124;178553123;178553122	chr2:179417851;179417850;179417849
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-147
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.1056
• 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/M	rs1553541468	None	1.0	N	0.693	0.484	0.605930529564	gnomAD-4.0.0	1.59624E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87054E-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	0.7123	likely_pathogenic	0.6234	pathogenic	-1.754	Destabilizing	0.999	D	0.603	neutral	N	0.507774311	None	None	N
V/C	0.9139	likely_pathogenic	0.8804	pathogenic	-1.702	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/D	0.9937	likely_pathogenic	0.988	pathogenic	-1.253	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/E	0.9814	likely_pathogenic	0.9665	pathogenic	-1.015	Destabilizing	1.0	D	0.866	deleterious	D	0.540137814	None	None	N
V/F	0.4689	ambiguous	0.3915	ambiguous	-0.977	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/G	0.8899	likely_pathogenic	0.8356	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.854	deleterious	N	0.495535514	None	None	N
V/H	0.9872	likely_pathogenic	0.9763	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/I	0.093	likely_benign	0.0912	benign	-0.192	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
V/K	0.9787	likely_pathogenic	0.9637	pathogenic	-1.216	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/L	0.4414	ambiguous	0.3923	ambiguous	-0.192	Destabilizing	0.997	D	0.611	neutral	N	0.486008725	None	None	N
V/M	0.4635	ambiguous	0.3946	ambiguous	-0.551	Destabilizing	1.0	D	0.693	prob.neutral	N	0.507536929	None	None	N
V/N	0.9759	likely_pathogenic	0.9602	pathogenic	-1.489	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/P	0.9892	likely_pathogenic	0.9825	pathogenic	-0.684	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/Q	0.972	likely_pathogenic	0.95	pathogenic	-1.23	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/R	0.9628	likely_pathogenic	0.9375	pathogenic	-1.316	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/S	0.9216	likely_pathogenic	0.878	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/T	0.8045	likely_pathogenic	0.734	pathogenic	-1.906	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
V/W	0.9832	likely_pathogenic	0.9691	pathogenic	-1.288	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9314	likely_pathogenic	0.8855	pathogenic	-0.925	Destabilizing	1.0	D	0.86	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.