TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26753	80482;80483;80484	chr2:178565875;178565874;178565873	chr2:179430602;179430601;179430600
N2AB	25112	75559;75560;75561	chr2:178565875;178565874;178565873	chr2:179430602;179430601;179430600
N2A	24185	72778;72779;72780	chr2:178565875;178565874;178565873	chr2:179430602;179430601;179430600
N2B	17688	53287;53288;53289	chr2:178565875;178565874;178565873	chr2:179430602;179430601;179430600
Novex-1	17813	53662;53663;53664	chr2:178565875;178565874;178565873	chr2:179430602;179430601;179430600
Novex-2	17880	53863;53864;53865	chr2:178565875;178565874;178565873	chr2:179430602;179430601;179430600
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: 71
• Structural Position: 104
• Q(SASA): 0.0864
• 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/S	rs1321131877	-3.377	1.0	D	0.874	0.838	0.939997187211	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Y/S	rs1321131877	-3.377	1.0	D	0.874	0.838	0.939997187211	gnomAD-4.0.0	6.36628E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57756E-06	1.43279E-05	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	0.9901	likely_pathogenic	0.9866	pathogenic	-3.092	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/C	0.7629	likely_pathogenic	0.7539	pathogenic	-1.613	Destabilizing	1.0	D	0.859	deleterious	D	0.683383304	None	None	N
Y/D	0.9954	likely_pathogenic	0.994	pathogenic	-3.277	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.683383304	None	None	N
Y/E	0.9987	likely_pathogenic	0.9981	pathogenic	-3.067	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/F	0.1507	likely_benign	0.1763	benign	-1.084	Destabilizing	0.44	N	0.541	neutral	D	0.61888261	None	None	N
Y/G	0.9795	likely_pathogenic	0.9702	pathogenic	-3.509	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/H	0.9179	likely_pathogenic	0.9108	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.813	deleterious	D	0.683383304	None	None	N
Y/I	0.9522	likely_pathogenic	0.9528	pathogenic	-1.705	Destabilizing	0.997	D	0.836	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.998	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/L	0.9303	likely_pathogenic	0.9272	pathogenic	-1.705	Destabilizing	0.982	D	0.798	deleterious	None	None	None	None	N
Y/M	0.9789	likely_pathogenic	0.9781	pathogenic	-1.408	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9474	likely_pathogenic	0.937	pathogenic	-2.817	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.6831815	None	None	N
Y/P	0.998	likely_pathogenic	0.9974	pathogenic	-2.183	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/Q	0.9952	likely_pathogenic	0.9935	pathogenic	-2.574	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/R	0.9917	likely_pathogenic	0.9892	pathogenic	-1.819	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/S	0.9452	likely_pathogenic	0.932	pathogenic	-3.191	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.683383304	None	None	N
Y/T	0.984	likely_pathogenic	0.982	pathogenic	-2.862	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/V	0.9204	likely_pathogenic	0.9184	pathogenic	-2.183	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
Y/W	0.7303	likely_pathogenic	0.7583	pathogenic	-0.345	Destabilizing	1.0	D	0.797	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.