TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5893	17902;17903;17904	chr2:178730988;178730987;178730986	chr2:179595715;179595714;179595713
N2AB	5576	16951;16952;16953	chr2:178730988;178730987;178730986	chr2:179595715;179595714;179595713
N2A	4649	14170;14171;14172	chr2:178730988;178730987;178730986	chr2:179595715;179595714;179595713
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-42
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1117
• 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	None	None	1.0	D	0.839	0.853	0.854161070543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.9966	likely_pathogenic	0.9982	pathogenic	-2.229	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/C	0.9632	likely_pathogenic	0.9825	pathogenic	-1.643	Destabilizing	1.0	D	0.839	deleterious	D	0.625331473	None	None	N
Y/D	0.9971	likely_pathogenic	0.9988	pathogenic	-2.766	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.625331473	None	None	N
Y/E	0.9987	likely_pathogenic	0.9994	pathogenic	-2.515	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/F	0.3218	likely_benign	0.3603	ambiguous	-0.726	Destabilizing	0.999	D	0.677	prob.neutral	D	0.577839519	None	None	N
Y/G	0.9919	likely_pathogenic	0.9958	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/H	0.9866	likely_pathogenic	0.9915	pathogenic	-1.946	Destabilizing	1.0	D	0.781	deleterious	D	0.625129669	None	None	N
Y/I	0.9346	likely_pathogenic	0.9472	pathogenic	-0.718	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9995	pathogenic	-1.856	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/L	0.9128	likely_pathogenic	0.938	pathogenic	-0.718	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
Y/M	0.9733	likely_pathogenic	0.983	pathogenic	-0.821	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
Y/N	0.984	likely_pathogenic	0.9913	pathogenic	-2.774	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.625331473	None	None	N
Y/P	0.9993	likely_pathogenic	0.9996	pathogenic	-1.237	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.9995	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/R	0.9971	likely_pathogenic	0.9984	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/S	0.9945	likely_pathogenic	0.997	pathogenic	-3.125	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.625331473	None	None	N
Y/T	0.9965	likely_pathogenic	0.9981	pathogenic	-2.724	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/V	0.9125	likely_pathogenic	0.9305	pathogenic	-1.237	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
Y/W	0.8882	likely_pathogenic	0.9018	pathogenic	-0.085	Destabilizing	1.0	D	0.781	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.