TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26815	80668;80669;80670	chr2:178565689;178565688;178565687	chr2:179430416;179430415;179430414
N2AB	25174	75745;75746;75747	chr2:178565689;178565688;178565687	chr2:179430416;179430415;179430414
N2A	24247	72964;72965;72966	chr2:178565689;178565688;178565687	chr2:179430416;179430415;179430414
N2B	17750	53473;53474;53475	chr2:178565689;178565688;178565687	chr2:179430416;179430415;179430414
Novex-1	17875	53848;53849;53850	chr2:178565689;178565688;178565687	chr2:179430416;179430415;179430414
Novex-2	17942	54049;54050;54051	chr2:178565689;178565688;178565687	chr2:179430416;179430415;179430414
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-83
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1406
• 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/D	None	None	1.0	D	0.905	0.87	0.937669560925	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	0.9959	likely_pathogenic	0.9953	pathogenic	-3.39	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/C	0.8954	likely_pathogenic	0.8695	pathogenic	-1.639	Destabilizing	1.0	D	0.865	deleterious	D	0.662102774	None	None	N
Y/D	0.9953	likely_pathogenic	0.9949	pathogenic	-3.707	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.662304578	None	None	N
Y/E	0.9987	likely_pathogenic	0.9986	pathogenic	-3.499	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/F	0.2383	likely_benign	0.2131	benign	-1.404	Destabilizing	0.999	D	0.646	neutral	D	0.568127887	None	None	N
Y/G	0.9892	likely_pathogenic	0.9871	pathogenic	-3.777	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
Y/H	0.9729	likely_pathogenic	0.9707	pathogenic	-2.506	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.64544764	None	None	N
Y/I	0.9723	likely_pathogenic	0.9678	pathogenic	-2.076	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.9986	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/L	0.9553	likely_pathogenic	0.9548	pathogenic	-2.076	Highly Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
Y/M	0.981	likely_pathogenic	0.9787	pathogenic	-1.694	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/N	0.9693	likely_pathogenic	0.9684	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.662102774	None	None	N
Y/P	0.9992	likely_pathogenic	0.9993	pathogenic	-2.533	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
Y/Q	0.9978	likely_pathogenic	0.9977	pathogenic	-2.823	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/R	0.9948	likely_pathogenic	0.9948	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/S	0.9837	likely_pathogenic	0.9823	pathogenic	-3.341	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.662102774	None	None	N
Y/T	0.9945	likely_pathogenic	0.9939	pathogenic	-3.022	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/V	0.9533	likely_pathogenic	0.9478	pathogenic	-2.533	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/W	0.8102	likely_pathogenic	0.8116	pathogenic	-0.674	Destabilizing	1.0	D	0.794	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.