TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18923	56992;56993;56994	chr2:178598943;178598942;178598941	chr2:179463670;179463669;179463668
N2AB	17282	52069;52070;52071	chr2:178598943;178598942;178598941	chr2:179463670;179463669;179463668
N2A	16355	49288;49289;49290	chr2:178598943;178598942;178598941	chr2:179463670;179463669;179463668
N2B	9858	29797;29798;29799	chr2:178598943;178598942;178598941	chr2:179463670;179463669;179463668
Novex-1	9983	30172;30173;30174	chr2:178598943;178598942;178598941	chr2:179463670;179463669;179463668
Novex-2	10050	30373;30374;30375	chr2:178598943;178598942;178598941	chr2:179463670;179463669;179463668
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-25
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1025
• 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
M/I	rs2052539328	None	0.017	N	0.375	0.139	0.379707525713	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/I	rs2052539328	None	0.017	N	0.375	0.139	0.379707525713	gnomAD-4.0.0	6.09062E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.02494E-06	0	3.40252E-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
M/A	0.6197	likely_pathogenic	0.6898	pathogenic	-1.966	Destabilizing	0.028	N	0.407	neutral	None	None	None	None	N
M/C	0.6316	likely_pathogenic	0.6219	pathogenic	-2.33	Highly Destabilizing	0.942	D	0.618	neutral	None	None	None	None	N
M/D	0.9922	likely_pathogenic	0.9922	pathogenic	-2.166	Highly Destabilizing	0.385	N	0.619	neutral	None	None	None	None	N
M/E	0.8119	likely_pathogenic	0.8225	pathogenic	-1.898	Destabilizing	0.119	N	0.511	neutral	None	None	None	None	N
M/F	0.4377	ambiguous	0.4806	ambiguous	-0.584	Destabilizing	0.428	N	0.569	neutral	None	None	None	None	N
M/G	0.8912	likely_pathogenic	0.9032	pathogenic	-2.464	Highly Destabilizing	0.385	N	0.564	neutral	None	None	None	None	N
M/H	0.7219	likely_pathogenic	0.7204	pathogenic	-2.239	Highly Destabilizing	0.842	D	0.641	neutral	None	None	None	None	N
M/I	0.4881	ambiguous	0.5588	ambiguous	-0.518	Destabilizing	0.017	N	0.375	neutral	N	0.421336257	None	None	N
M/K	0.2776	likely_benign	0.2505	benign	-1.357	Destabilizing	0.001	N	0.255	neutral	N	0.377873481	None	None	N
M/L	0.2006	likely_benign	0.2267	benign	-0.518	Destabilizing	None	N	0.136	neutral	N	0.427664796	None	None	N
M/N	0.8846	likely_pathogenic	0.8978	pathogenic	-1.903	Destabilizing	0.236	N	0.567	neutral	None	None	None	None	N
M/P	0.999	likely_pathogenic	0.9992	pathogenic	-0.985	Destabilizing	0.822	D	0.637	neutral	None	None	None	None	N
M/Q	0.343	ambiguous	0.3398	benign	-1.51	Destabilizing	0.236	N	0.481	neutral	None	None	None	None	N
M/R	0.3008	likely_benign	0.2889	benign	-1.586	Destabilizing	None	N	0.278	neutral	N	0.352804465	None	None	N
M/S	0.7556	likely_pathogenic	0.7966	pathogenic	-2.373	Highly Destabilizing	0.119	N	0.427	neutral	None	None	None	None	N
M/T	0.5049	ambiguous	0.5619	ambiguous	-1.971	Destabilizing	0.092	N	0.428	neutral	N	0.470879643	None	None	N
M/V	0.1559	likely_benign	0.1818	benign	-0.985	Destabilizing	None	N	0.161	neutral	N	0.412311342	None	None	N
M/W	0.7585	likely_pathogenic	0.78	pathogenic	-0.994	Destabilizing	0.942	D	0.621	neutral	None	None	None	None	N
M/Y	0.6118	likely_pathogenic	0.6393	pathogenic	-0.914	Destabilizing	0.603	D	0.609	neutral	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.