TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27540	82843;82844;82845	chr2:178563514;178563513;178563512	chr2:179428241;179428240;179428239
N2AB	25899	77920;77921;77922	chr2:178563514;178563513;178563512	chr2:179428241;179428240;179428239
N2A	24972	75139;75140;75141	chr2:178563514;178563513;178563512	chr2:179428241;179428240;179428239
N2B	18475	55648;55649;55650	chr2:178563514;178563513;178563512	chr2:179428241;179428240;179428239
Novex-1	18600	56023;56024;56025	chr2:178563514;178563513;178563512	chr2:179428241;179428240;179428239
Novex-2	18667	56224;56225;56226	chr2:178563514;178563513;178563512	chr2:179428241;179428240;179428239
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: Fn3-88
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1058
• 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
Y/C	rs913135593	-2.114	1.0	D	0.857	0.802	0.868516351601	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Y/C	rs913135593	-2.114	1.0	D	0.857	0.802	0.868516351601	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs913135593	-2.114	1.0	D	0.857	0.802	0.868516351601	gnomAD-4.0.0	3.84341E-06	None	None	None	None	N	None	5.07425E-05	0	None	0	0	None	0	0	0	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	0.9802	likely_pathogenic	0.988	pathogenic	-3.291	Highly Destabilizing	0.991	D	0.842	deleterious	None	None	None	None	N
Y/C	0.6989	likely_pathogenic	0.7784	pathogenic	-1.83	Destabilizing	1.0	D	0.857	deleterious	D	0.657148698	None	None	N
Y/D	0.9897	likely_pathogenic	0.9928	pathogenic	-3.643	Highly Destabilizing	0.999	D	0.885	deleterious	D	0.657380863	None	None	N
Y/E	0.9955	likely_pathogenic	0.9973	pathogenic	-3.438	Highly Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
Y/F	0.2013	likely_benign	0.2678	benign	-1.223	Destabilizing	0.117	N	0.536	neutral	D	0.615864469	None	None	N
Y/G	0.9739	likely_pathogenic	0.9786	pathogenic	-3.698	Highly Destabilizing	0.998	D	0.886	deleterious	None	None	None	None	N
Y/H	0.921	likely_pathogenic	0.9526	pathogenic	-2.309	Highly Destabilizing	0.999	D	0.813	deleterious	D	0.689419585	None	None	N
Y/I	0.9156	likely_pathogenic	0.9418	pathogenic	-1.923	Destabilizing	0.99	D	0.836	deleterious	None	None	None	None	N
Y/K	0.9954	likely_pathogenic	0.9973	pathogenic	-2.281	Highly Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
Y/L	0.8807	likely_pathogenic	0.8957	pathogenic	-1.923	Destabilizing	0.966	D	0.791	deleterious	None	None	None	None	N
Y/M	0.9444	likely_pathogenic	0.9643	pathogenic	-1.619	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
Y/N	0.943	likely_pathogenic	0.9607	pathogenic	-3.058	Highly Destabilizing	0.999	D	0.863	deleterious	D	0.663679669	None	None	N
Y/P	0.9973	likely_pathogenic	0.9975	pathogenic	-2.396	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9906	likely_pathogenic	0.9948	pathogenic	-2.822	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
Y/R	0.9808	likely_pathogenic	0.9863	pathogenic	-2.0	Highly Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
Y/S	0.9366	likely_pathogenic	0.9563	pathogenic	-3.389	Highly Destabilizing	0.997	D	0.875	deleterious	D	0.689419585	None	None	N
Y/T	0.9716	likely_pathogenic	0.9833	pathogenic	-3.068	Highly Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
Y/V	0.791	likely_pathogenic	0.856	pathogenic	-2.396	Highly Destabilizing	0.983	D	0.816	deleterious	None	None	None	None	N
Y/W	0.6513	likely_pathogenic	0.7269	pathogenic	-0.531	Destabilizing	1.0	D	0.797	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.