TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32866	98821;98822;98823	chr2:178539469;178539468;178539467	chr2:179404196;179404195;179404194
N2AB	31225	93898;93899;93900	chr2:178539469;178539468;178539467	chr2:179404196;179404195;179404194
N2A	30298	91117;91118;91119	chr2:178539469;178539468;178539467	chr2:179404196;179404195;179404194
N2B	23801	71626;71627;71628	chr2:178539469;178539468;178539467	chr2:179404196;179404195;179404194
Novex-1	23926	72001;72002;72003	chr2:178539469;178539468;178539467	chr2:179404196;179404195;179404194
Novex-2	23993	72202;72203;72204	chr2:178539469;178539468;178539467	chr2:179404196;179404195;179404194
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: Fn3-127
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.07
• 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	0.887	0.928	0.928776056712	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	0.996	likely_pathogenic	0.9923	pathogenic	-3.379	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/C	0.942	likely_pathogenic	0.886	pathogenic	-1.818	Destabilizing	1.0	D	0.887	deleterious	D	0.686865774	None	None	N
Y/D	0.9934	likely_pathogenic	0.9899	pathogenic	-3.927	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.686865774	None	None	N
Y/E	0.9982	likely_pathogenic	0.9971	pathogenic	-3.715	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/F	0.3683	ambiguous	0.3198	benign	-1.485	Destabilizing	0.999	D	0.741	deleterious	D	0.639777428	None	None	N
Y/G	0.9871	likely_pathogenic	0.9777	pathogenic	-3.77	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/H	0.9765	likely_pathogenic	0.9571	pathogenic	-2.55	Highly Destabilizing	1.0	D	0.816	deleterious	D	0.686865774	None	None	N
Y/I	0.972	likely_pathogenic	0.9563	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.9977	pathogenic	-2.653	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/L	0.9674	likely_pathogenic	0.951	pathogenic	-2.044	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
Y/M	0.9852	likely_pathogenic	0.9744	pathogenic	-1.673	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/N	0.9557	likely_pathogenic	0.9283	pathogenic	-3.509	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.686663969	None	None	N
Y/P	0.9994	likely_pathogenic	0.9991	pathogenic	-2.509	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/Q	0.9978	likely_pathogenic	0.9957	pathogenic	-3.227	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/R	0.9965	likely_pathogenic	0.9943	pathogenic	-2.451	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/S	0.9847	likely_pathogenic	0.9722	pathogenic	-3.737	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.686865774	None	None	N
Y/T	0.9935	likely_pathogenic	0.9878	pathogenic	-3.411	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/V	0.9507	likely_pathogenic	0.9264	pathogenic	-2.509	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/W	0.8828	likely_pathogenic	0.8602	pathogenic	-0.785	Destabilizing	1.0	D	0.803	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.