TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34265	103018;103019;103020	chr2:178533822;178533821;178533820	chr2:179398549;179398548;179398547
N2AB	32624	98095;98096;98097	chr2:178533822;178533821;178533820	chr2:179398549;179398548;179398547
N2A	31697	95314;95315;95316	chr2:178533822;178533821;178533820	chr2:179398549;179398548;179398547
N2B	25200	75823;75824;75825	chr2:178533822;178533821;178533820	chr2:179398549;179398548;179398547
Novex-1	25325	76198;76199;76200	chr2:178533822;178533821;178533820	chr2:179398549;179398548;179398547
Novex-2	25392	76399;76400;76401	chr2:178533822;178533821;178533820	chr2:179398549;179398548;179398547
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-161
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4011
• 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
Y/C	rs1559030437	None	0.026	N	0.305	0.323	0.369867359543	gnomAD-4.0.0	5.47324E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19525E-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
Y/A	0.6293	likely_pathogenic	0.7713	pathogenic	-1.373	Destabilizing	0.851	D	0.563	neutral	None	None	None	None	I
Y/C	0.1548	likely_benign	0.2708	benign	-0.535	Destabilizing	0.026	N	0.305	neutral	N	0.483188084	None	None	I
Y/D	0.6526	likely_pathogenic	0.7594	pathogenic	-0.003	Destabilizing	0.995	D	0.677	prob.neutral	N	0.468237274	None	None	I
Y/E	0.8164	likely_pathogenic	0.8812	pathogenic	0.053	Stabilizing	0.996	D	0.669	neutral	None	None	None	None	I
Y/F	0.1109	likely_benign	0.1297	benign	-0.493	Destabilizing	0.026	N	0.226	neutral	N	0.475203319	None	None	I
Y/G	0.5311	ambiguous	0.6974	pathogenic	-1.63	Destabilizing	0.988	D	0.583	neutral	None	None	None	None	I
Y/H	0.3307	likely_benign	0.4183	ambiguous	-0.204	Destabilizing	0.995	D	0.541	neutral	N	0.482494651	None	None	I
Y/I	0.6042	likely_pathogenic	0.7248	pathogenic	-0.638	Destabilizing	0.952	D	0.558	neutral	None	None	None	None	I
Y/K	0.7883	likely_pathogenic	0.85	pathogenic	-0.592	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	I
Y/L	0.5334	ambiguous	0.6366	pathogenic	-0.638	Destabilizing	0.851	D	0.549	neutral	None	None	None	None	I
Y/M	0.7299	likely_pathogenic	0.8179	pathogenic	-0.617	Destabilizing	0.997	D	0.62	neutral	None	None	None	None	I
Y/N	0.3863	ambiguous	0.5245	ambiguous	-0.992	Destabilizing	0.995	D	0.669	neutral	N	0.455750767	None	None	I
Y/P	0.8704	likely_pathogenic	0.9058	pathogenic	-0.872	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	I
Y/Q	0.6563	likely_pathogenic	0.7644	pathogenic	-0.857	Destabilizing	0.996	D	0.623	neutral	None	None	None	None	I
Y/R	0.576	likely_pathogenic	0.6705	pathogenic	-0.331	Destabilizing	0.996	D	0.669	neutral	None	None	None	None	I
Y/S	0.3323	likely_benign	0.4935	ambiguous	-1.419	Destabilizing	0.968	D	0.555	neutral	N	0.413690714	None	None	I
Y/T	0.5922	likely_pathogenic	0.7566	pathogenic	-1.266	Destabilizing	0.976	D	0.567	neutral	None	None	None	None	I
Y/V	0.4475	ambiguous	0.5814	pathogenic	-0.872	Destabilizing	0.919	D	0.571	neutral	None	None	None	None	I
Y/W	0.5079	ambiguous	0.544	ambiguous	-0.315	Destabilizing	0.999	D	0.537	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.