TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2917	8974;8975;8976	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557
N2AB	2917	8974;8975;8976	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557
N2A	2917	8974;8975;8976	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557
N2B	2871	8836;8837;8838	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557
Novex-1	2871	8836;8837;8838	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557
Novex-2	2871	8836;8837;8838	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557
Novex-3	2917	8974;8975;8976	chr2:178769832;178769831;178769830	chr2:179634559;179634558;179634557

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-19
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.3115
• 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
N/S	rs1420302039	None	0.953	D	0.461	0.603	0.435152311215	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1420302039	None	0.953	D	0.461	0.603	0.435152311215	gnomAD-4.0.0	6.5735E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4702E-05	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
N/A	0.7359	likely_pathogenic	0.6097	pathogenic	-0.592	Destabilizing	0.993	D	0.539	neutral	None	None	None	None	N
N/C	0.7775	likely_pathogenic	0.7006	pathogenic	0.197	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
N/D	0.1738	likely_benign	0.1493	benign	0.125	Stabilizing	0.061	N	0.191	neutral	N	0.479614411	None	None	N
N/E	0.7661	likely_pathogenic	0.658	pathogenic	0.143	Stabilizing	0.931	D	0.439	neutral	None	None	None	None	N
N/F	0.9669	likely_pathogenic	0.9342	pathogenic	-0.718	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
N/G	0.4659	ambiguous	0.4303	ambiguous	-0.837	Destabilizing	0.982	D	0.437	neutral	None	None	None	None	N
N/H	0.3605	ambiguous	0.291	benign	-0.733	Destabilizing	0.999	D	0.456	neutral	D	0.725246645	None	None	N
N/I	0.9591	likely_pathogenic	0.9102	pathogenic	-0.016	Destabilizing	0.999	D	0.62	neutral	D	0.725684273	None	None	N
N/K	0.7126	likely_pathogenic	0.59	pathogenic	-0.052	Destabilizing	0.99	D	0.427	neutral	D	0.645675834	None	None	N
N/L	0.8831	likely_pathogenic	0.8052	pathogenic	-0.016	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
N/M	0.8915	likely_pathogenic	0.8159	pathogenic	0.268	Stabilizing	1.0	D	0.583	neutral	None	None	None	None	N
N/P	0.9971	likely_pathogenic	0.995	pathogenic	-0.18	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
N/Q	0.709	likely_pathogenic	0.609	pathogenic	-0.502	Destabilizing	0.998	D	0.409	neutral	None	None	None	None	N
N/R	0.7772	likely_pathogenic	0.6748	pathogenic	-0.044	Destabilizing	0.998	D	0.404	neutral	None	None	None	None	N
N/S	0.2491	likely_benign	0.1992	benign	-0.422	Destabilizing	0.953	D	0.461	neutral	D	0.646677628	None	None	N
N/T	0.8067	likely_pathogenic	0.6864	pathogenic	-0.234	Destabilizing	0.99	D	0.408	neutral	D	0.724602792	None	None	N
N/V	0.9434	likely_pathogenic	0.8831	pathogenic	-0.18	Destabilizing	0.999	D	0.612	neutral	None	None	None	None	N
N/W	0.9801	likely_pathogenic	0.9678	pathogenic	-0.608	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
N/Y	0.6154	likely_pathogenic	0.4838	ambiguous	-0.381	Destabilizing	0.999	D	0.569	neutral	D	0.725323814	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.