TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8870	26833;26834;26835	chr2:178714050;178714049;178714048	chr2:179578777;179578776;179578775
N2AB	8553	25882;25883;25884	chr2:178714050;178714049;178714048	chr2:179578777;179578776;179578775
N2A	7626	23101;23102;23103	chr2:178714050;178714049;178714048	chr2:179578777;179578776;179578775
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-74
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2007
• 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
L/I	None	None	0.015	N	0.353	0.09	0.267755039894	gnomAD-4.0.0	1.20032E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.7777	likely_pathogenic	0.819	pathogenic	-2.044	Highly Destabilizing	0.25	N	0.529	neutral	None	None	None	None	N
L/C	0.8063	likely_pathogenic	0.8467	pathogenic	-1.18	Destabilizing	0.982	D	0.764	deleterious	None	None	None	None	N
L/D	0.988	likely_pathogenic	0.9919	pathogenic	-2.527	Highly Destabilizing	0.826	D	0.851	deleterious	None	None	None	None	N
L/E	0.9088	likely_pathogenic	0.9356	pathogenic	-2.24	Highly Destabilizing	0.826	D	0.835	deleterious	None	None	None	None	N
L/F	0.348	ambiguous	0.4294	ambiguous	-1.222	Destabilizing	0.7	D	0.682	prob.neutral	None	None	None	None	N
L/G	0.9472	likely_pathogenic	0.9583	pathogenic	-2.604	Highly Destabilizing	0.7	D	0.828	deleterious	None	None	None	None	N
L/H	0.8208	likely_pathogenic	0.8688	pathogenic	-2.209	Highly Destabilizing	0.982	D	0.849	deleterious	None	None	None	None	N
L/I	0.0843	likely_benign	0.0891	benign	-0.4	Destabilizing	0.015	N	0.353	neutral	N	0.472571233	None	None	N
L/K	0.8132	likely_pathogenic	0.8476	pathogenic	-1.462	Destabilizing	0.7	D	0.781	deleterious	None	None	None	None	N
L/M	0.1655	likely_benign	0.1849	benign	-0.414	Destabilizing	0.045	N	0.448	neutral	None	None	None	None	N
L/N	0.9382	likely_pathogenic	0.9482	pathogenic	-2.032	Highly Destabilizing	0.826	D	0.851	deleterious	None	None	None	None	N
L/P	0.9542	likely_pathogenic	0.9667	pathogenic	-0.933	Destabilizing	0.916	D	0.851	deleterious	D	0.526395788	None	None	N
L/Q	0.6999	likely_pathogenic	0.766	pathogenic	-1.747	Destabilizing	0.638	D	0.822	deleterious	D	0.539980592	None	None	N
L/R	0.7198	likely_pathogenic	0.7731	pathogenic	-1.533	Destabilizing	0.638	D	0.819	deleterious	D	0.535941668	None	None	N
L/S	0.9268	likely_pathogenic	0.9479	pathogenic	-2.638	Highly Destabilizing	0.7	D	0.755	deleterious	None	None	None	None	N
L/T	0.7872	likely_pathogenic	0.8273	pathogenic	-2.188	Highly Destabilizing	0.7	D	0.691	prob.neutral	None	None	None	None	N
L/V	0.1233	likely_benign	0.1402	benign	-0.933	Destabilizing	0.094	N	0.49	neutral	D	0.5348332	None	None	N
L/W	0.6506	likely_pathogenic	0.7395	pathogenic	-1.612	Destabilizing	0.982	D	0.801	deleterious	None	None	None	None	N
L/Y	0.7444	likely_pathogenic	0.8038	pathogenic	-1.249	Destabilizing	0.826	D	0.791	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.