TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34195	102808;102809;102810	chr2:178534032;178534031;178534030	chr2:179398759;179398758;179398757
N2AB	32554	97885;97886;97887	chr2:178534032;178534031;178534030	chr2:179398759;179398758;179398757
N2A	31627	95104;95105;95106	chr2:178534032;178534031;178534030	chr2:179398759;179398758;179398757
N2B	25130	75613;75614;75615	chr2:178534032;178534031;178534030	chr2:179398759;179398758;179398757
Novex-1	25255	75988;75989;75990	chr2:178534032;178534031;178534030	chr2:179398759;179398758;179398757
Novex-2	25322	76189;76190;76191	chr2:178534032;178534031;178534030	chr2:179398759;179398758;179398757
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-160
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2991
• 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	0.999	D	0.665	0.385	0.622351988405	gnomAD-4.0.0	3.18197E-06	None	None	None	None	N	None	0	0	None	0	2.77254E-05	None	0	0	2.85767E-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	0.4933	ambiguous	0.5559	ambiguous	-2.717	Highly Destabilizing	0.851	D	0.579	neutral	None	None	None	None	N
Y/C	0.1878	likely_benign	0.2531	benign	-1.079	Destabilizing	0.999	D	0.665	neutral	D	0.522245118	None	None	N
Y/D	0.3481	ambiguous	0.429	ambiguous	-1.72	Destabilizing	0.968	D	0.662	neutral	N	0.484284162	None	None	N
Y/E	0.5429	ambiguous	0.5997	pathogenic	-1.617	Destabilizing	0.919	D	0.618	neutral	None	None	None	None	N
Y/F	0.1205	likely_benign	0.1301	benign	-1.154	Destabilizing	0.946	D	0.546	neutral	N	0.472989733	None	None	N
Y/G	0.5712	likely_pathogenic	0.6328	pathogenic	-3.055	Highly Destabilizing	0.919	D	0.627	neutral	None	None	None	None	N
Y/H	0.1133	likely_benign	0.1258	benign	-1.426	Destabilizing	0.995	D	0.617	neutral	N	0.478531626	None	None	N
Y/I	0.4397	ambiguous	0.4604	ambiguous	-1.655	Destabilizing	0.976	D	0.623	neutral	None	None	None	None	N
Y/K	0.4889	ambiguous	0.5229	ambiguous	-1.526	Destabilizing	0.851	D	0.582	neutral	None	None	None	None	N
Y/L	0.399	ambiguous	0.4249	ambiguous	-1.655	Destabilizing	0.851	D	0.542	neutral	None	None	None	None	N
Y/M	0.5536	ambiguous	0.5724	pathogenic	-1.162	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
Y/N	0.1622	likely_benign	0.1964	benign	-1.855	Destabilizing	0.968	D	0.641	neutral	N	0.484284162	None	None	N
Y/P	0.9801	likely_pathogenic	0.9849	pathogenic	-2.01	Highly Destabilizing	0.988	D	0.691	prob.neutral	None	None	None	None	N
Y/Q	0.4066	ambiguous	0.455	ambiguous	-1.798	Destabilizing	0.976	D	0.645	neutral	None	None	None	None	N
Y/R	0.3296	likely_benign	0.3572	ambiguous	-1.021	Destabilizing	0.076	N	0.5	neutral	None	None	None	None	N
Y/S	0.1827	likely_benign	0.211	benign	-2.333	Highly Destabilizing	0.811	D	0.573	neutral	N	0.477664834	None	None	N
Y/T	0.3023	likely_benign	0.3389	benign	-2.139	Highly Destabilizing	0.132	N	0.475	neutral	None	None	None	None	N
Y/V	0.3484	ambiguous	0.3681	ambiguous	-2.01	Highly Destabilizing	0.851	D	0.522	neutral	None	None	None	None	N
Y/W	0.4186	ambiguous	0.4389	ambiguous	-0.666	Destabilizing	0.999	D	0.607	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.