TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17506	52741;52742;52743	chr2:178608367;178608366;178608365	chr2:179473094;179473093;179473092
N2AB	15865	47818;47819;47820	chr2:178608367;178608366;178608365	chr2:179473094;179473093;179473092
N2A	14938	45037;45038;45039	chr2:178608367;178608366;178608365	chr2:179473094;179473093;179473092
N2B	8441	25546;25547;25548	chr2:178608367;178608366;178608365	chr2:179473094;179473093;179473092
Novex-1	8566	25921;25922;25923	chr2:178608367;178608366;178608365	chr2:179473094;179473093;179473092
Novex-2	8633	26122;26123;26124	chr2:178608367;178608366;178608365	chr2:179473094;179473093;179473092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-15
• Domain position: 37
• Structural Position: 40
• Q(SASA): 0.1231
• 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	0.005	N	0.242	0.065	0.335164054921	gnomAD-4.0.0	1.36993E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32385E-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
L/A	0.908	likely_pathogenic	0.9235	pathogenic	-3.047	Highly Destabilizing	0.688	D	0.627	neutral	None	None	None	None	N
L/C	0.9173	likely_pathogenic	0.9338	pathogenic	-2.048	Highly Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9994	pathogenic	-3.841	Highly Destabilizing	0.991	D	0.854	deleterious	None	None	None	None	N
L/E	0.9935	likely_pathogenic	0.9932	pathogenic	-3.527	Highly Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	N
L/F	0.8488	likely_pathogenic	0.8512	pathogenic	-1.921	Destabilizing	0.934	D	0.673	neutral	N	0.503710316	None	None	N
L/G	0.9917	likely_pathogenic	0.9928	pathogenic	-3.631	Highly Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
L/H	0.9942	likely_pathogenic	0.9938	pathogenic	-3.216	Highly Destabilizing	0.997	D	0.851	deleterious	N	0.503963806	None	None	N
L/I	0.0849	likely_benign	0.101	benign	-1.276	Destabilizing	0.005	N	0.242	neutral	N	0.386700821	None	None	N
L/K	0.9923	likely_pathogenic	0.9899	pathogenic	-2.57	Highly Destabilizing	0.974	D	0.775	deleterious	None	None	None	None	N
L/M	0.3226	likely_benign	0.3231	benign	-1.234	Destabilizing	0.949	D	0.595	neutral	None	None	None	None	N
L/N	0.9962	likely_pathogenic	0.9961	pathogenic	-3.303	Highly Destabilizing	0.991	D	0.857	deleterious	None	None	None	None	N
L/P	0.9936	likely_pathogenic	0.995	pathogenic	-1.859	Destabilizing	0.989	D	0.855	deleterious	N	0.492442916	None	None	N
L/Q	0.9854	likely_pathogenic	0.9826	pathogenic	-2.982	Highly Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
L/R	0.9873	likely_pathogenic	0.9851	pathogenic	-2.468	Highly Destabilizing	0.989	D	0.831	deleterious	N	0.503963806	None	None	N
L/S	0.9917	likely_pathogenic	0.9934	pathogenic	-3.816	Highly Destabilizing	0.915	D	0.761	deleterious	None	None	None	None	N
L/T	0.921	likely_pathogenic	0.9296	pathogenic	-3.349	Highly Destabilizing	0.842	D	0.625	neutral	None	None	None	None	N
L/V	0.1056	likely_benign	0.1289	benign	-1.859	Destabilizing	0.007	N	0.265	neutral	N	0.364242462	None	None	N
L/W	0.9842	likely_pathogenic	0.983	pathogenic	-2.338	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
L/Y	0.9865	likely_pathogenic	0.9847	pathogenic	-2.146	Highly Destabilizing	0.991	D	0.738	prob.delet.	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.