TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26718	80377;80378;80379	chr2:178565980;178565979;178565978	chr2:179430707;179430706;179430705
N2AB	25077	75454;75455;75456	chr2:178565980;178565979;178565978	chr2:179430707;179430706;179430705
N2A	24150	72673;72674;72675	chr2:178565980;178565979;178565978	chr2:179430707;179430706;179430705
N2B	17653	53182;53183;53184	chr2:178565980;178565979;178565978	chr2:179430707;179430706;179430705
Novex-1	17778	53557;53558;53559	chr2:178565980;178565979;178565978	chr2:179430707;179430706;179430705
Novex-2	17845	53758;53759;53760	chr2:178565980;178565979;178565978	chr2:179430707;179430706;179430705
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: Fn3-82
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1213
• 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	rs1705690461	None	1.0	D	0.881	0.874	0.868257853576	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1705690461	None	1.0	D	0.881	0.874	0.868257853576	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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	0.9957	likely_pathogenic	0.9966	pathogenic	-3.528	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/C	0.9242	likely_pathogenic	0.9381	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.658602457	None	None	N
Y/D	0.9967	likely_pathogenic	0.9964	pathogenic	-3.89	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.659006066	None	None	N
Y/E	0.9992	likely_pathogenic	0.9993	pathogenic	-3.685	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/F	0.1965	likely_benign	0.2099	benign	-1.311	Destabilizing	0.999	D	0.634	neutral	D	0.592871295	None	None	N
Y/G	0.9919	likely_pathogenic	0.9922	pathogenic	-3.932	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/H	0.9668	likely_pathogenic	0.971	pathogenic	-2.522	Highly Destabilizing	1.0	D	0.793	deleterious	D	0.658602457	None	None	N
Y/I	0.9655	likely_pathogenic	0.9737	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.999	pathogenic	-2.451	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/L	0.9451	likely_pathogenic	0.9539	pathogenic	-2.159	Highly Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
Y/M	0.9817	likely_pathogenic	0.9866	pathogenic	-1.979	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/N	0.9784	likely_pathogenic	0.9792	pathogenic	-3.224	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.659006066	None	None	N
Y/P	0.9992	likely_pathogenic	0.9993	pathogenic	-2.634	Highly Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
Y/Q	0.9982	likely_pathogenic	0.9985	pathogenic	-2.994	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9942	likely_pathogenic	0.9952	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/S	0.986	likely_pathogenic	0.9875	pathogenic	-3.566	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.659006066	None	None	N
Y/T	0.9939	likely_pathogenic	0.9947	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/V	0.9458	likely_pathogenic	0.9588	pathogenic	-2.634	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
Y/W	0.8191	likely_pathogenic	0.8426	pathogenic	-0.572	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.