TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27642	83149;83150;83151	chr2:178563208;178563207;178563206	chr2:179427935;179427934;179427933
N2AB	26001	78226;78227;78228	chr2:178563208;178563207;178563206	chr2:179427935;179427934;179427933
N2A	25074	75445;75446;75447	chr2:178563208;178563207;178563206	chr2:179427935;179427934;179427933
N2B	18577	55954;55955;55956	chr2:178563208;178563207;178563206	chr2:179427935;179427934;179427933
Novex-1	18702	56329;56330;56331	chr2:178563208;178563207;178563206	chr2:179427935;179427934;179427933
Novex-2	18769	56530;56531;56532	chr2:178563208;178563207;178563206	chr2:179427935;179427934;179427933
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: Fn3-89
• Domain position: 73
• Structural Position: 104
• Q(SASA): 0.1207
• 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	0.875	0.914	0.920292468266	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	0.9845	likely_pathogenic	0.9822	pathogenic	-3.003	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/C	0.8097	likely_pathogenic	0.7821	pathogenic	-1.657	Destabilizing	1.0	D	0.875	deleterious	D	0.655987875	None	None	N
Y/D	0.9875	likely_pathogenic	0.987	pathogenic	-3.508	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.688026597	None	None	N
Y/E	0.9951	likely_pathogenic	0.9949	pathogenic	-3.291	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/F	0.2556	likely_benign	0.2556	benign	-0.997	Destabilizing	0.999	D	0.761	deleterious	D	0.60193459	None	None	N
Y/G	0.9642	likely_pathogenic	0.9607	pathogenic	-3.424	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/H	0.926	likely_pathogenic	0.9164	pathogenic	-2.152	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.688026597	None	None	N
Y/I	0.9342	likely_pathogenic	0.9177	pathogenic	-1.598	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.994	likely_pathogenic	0.9931	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/L	0.919	likely_pathogenic	0.8954	pathogenic	-1.598	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
Y/M	0.9457	likely_pathogenic	0.9397	pathogenic	-1.408	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/N	0.9041	likely_pathogenic	0.8969	pathogenic	-2.891	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.687824793	None	None	N
Y/P	0.9988	likely_pathogenic	0.9986	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/Q	0.9904	likely_pathogenic	0.9897	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/R	0.9863	likely_pathogenic	0.9843	pathogenic	-1.907	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/S	0.9662	likely_pathogenic	0.9647	pathogenic	-3.201	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.688026597	None	None	N
Y/T	0.9816	likely_pathogenic	0.9812	pathogenic	-2.859	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/V	0.8841	likely_pathogenic	0.8646	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/W	0.7919	likely_pathogenic	0.7836	pathogenic	-0.291	Destabilizing	1.0	D	0.811	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.