TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20207	60844;60845;60846	chr2:178591106;178591105;178591104	chr2:179455833;179455832;179455831
N2AB	18566	55921;55922;55923	chr2:178591106;178591105;178591104	chr2:179455833;179455832;179455831
N2A	17639	53140;53141;53142	chr2:178591106;178591105;178591104	chr2:179455833;179455832;179455831
N2B	11142	33649;33650;33651	chr2:178591106;178591105;178591104	chr2:179455833;179455832;179455831
Novex-1	11267	34024;34025;34026	chr2:178591106;178591105;178591104	chr2:179455833;179455832;179455831
Novex-2	11334	34225;34226;34227	chr2:178591106;178591105;178591104	chr2:179455833;179455832;179455831
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: Fn3-34
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.116
• 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/H	None	None	1.0	D	0.823	0.82	0.748493183723	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9937	likely_pathogenic	0.9976	pathogenic	-3.562	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/C	0.8774	likely_pathogenic	0.9416	pathogenic	-2.498	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.648155048	None	None	N
Y/D	0.99	likely_pathogenic	0.997	pathogenic	-3.828	Highly Destabilizing	1.0	D	0.923	deleterious	D	0.648558656	None	None	N
Y/E	0.9983	likely_pathogenic	0.9994	pathogenic	-3.626	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
Y/F	0.3174	likely_benign	0.36	ambiguous	-1.356	Destabilizing	0.999	D	0.645	neutral	D	0.545045377	None	None	N
Y/G	0.9828	likely_pathogenic	0.9927	pathogenic	-3.969	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/H	0.9584	likely_pathogenic	0.9807	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.648155048	None	None	N
Y/I	0.9632	likely_pathogenic	0.9781	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.999	pathogenic	-2.443	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
Y/L	0.9335	likely_pathogenic	0.9581	pathogenic	-2.192	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Y/M	0.9815	likely_pathogenic	0.9898	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/N	0.957	likely_pathogenic	0.9824	pathogenic	-3.185	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.648558656	None	None	N
Y/P	0.9983	likely_pathogenic	0.9995	pathogenic	-2.666	Highly Destabilizing	1.0	D	0.946	deleterious	None	None	None	None	N
Y/Q	0.9969	likely_pathogenic	0.9988	pathogenic	-2.974	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/R	0.9908	likely_pathogenic	0.9955	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/S	0.9741	likely_pathogenic	0.9907	pathogenic	-3.579	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.648558656	None	None	N
Y/T	0.9883	likely_pathogenic	0.9957	pathogenic	-3.253	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
Y/V	0.9328	likely_pathogenic	0.9618	pathogenic	-2.666	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Y/W	0.8593	likely_pathogenic	0.89	pathogenic	-0.572	Destabilizing	1.0	D	0.803	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.