TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8177	24754;24755;24756	chr2:178718577;178718576;178718575	chr2:179583304;179583303;179583302
N2AB	7860	23803;23804;23805	chr2:178718577;178718576;178718575	chr2:179583304;179583303;179583302
N2A	6933	21022;21023;21024	chr2:178718577;178718576;178718575	chr2:179583304;179583303;179583302
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-67
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2269
• 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/W	None	None	0.999	N	0.643	0.404	0.798450862424	gnomAD-4.0.0	1.59417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43488E-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	0.8134	likely_pathogenic	0.7971	pathogenic	-2.189	Highly Destabilizing	0.863	D	0.515	neutral	None	None	None	None	N
L/C	0.9276	likely_pathogenic	0.9054	pathogenic	-1.298	Destabilizing	0.1	N	0.451	neutral	None	None	None	None	N
L/D	0.9965	likely_pathogenic	0.9946	pathogenic	-1.785	Destabilizing	0.991	D	0.728	prob.delet.	None	None	None	None	N
L/E	0.978	likely_pathogenic	0.9704	pathogenic	-1.644	Destabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	N
L/F	0.5744	likely_pathogenic	0.5313	ambiguous	-1.295	Destabilizing	0.077	N	0.339	neutral	N	0.495489157	None	None	N
L/G	0.9694	likely_pathogenic	0.9613	pathogenic	-2.666	Highly Destabilizing	0.969	D	0.669	neutral	None	None	None	None	N
L/H	0.9658	likely_pathogenic	0.9496	pathogenic	-1.906	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
L/I	0.2029	likely_benign	0.1806	benign	-0.864	Destabilizing	0.759	D	0.455	neutral	None	None	None	None	N
L/K	0.9718	likely_pathogenic	0.9611	pathogenic	-1.494	Destabilizing	0.884	D	0.619	neutral	None	None	None	None	N
L/M	0.2154	likely_benign	0.2058	benign	-0.686	Destabilizing	0.988	D	0.609	neutral	N	0.482411332	None	None	N
L/N	0.9762	likely_pathogenic	0.9655	pathogenic	-1.527	Destabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	N
L/P	0.6509	likely_pathogenic	0.574	pathogenic	-1.281	Destabilizing	0.046	N	0.543	neutral	None	None	None	None	N
L/Q	0.922	likely_pathogenic	0.8992	pathogenic	-1.521	Destabilizing	0.982	D	0.691	prob.neutral	None	None	None	None	N
L/R	0.9592	likely_pathogenic	0.9437	pathogenic	-1.092	Destabilizing	0.1	N	0.491	neutral	None	None	None	None	N
L/S	0.9608	likely_pathogenic	0.9511	pathogenic	-2.269	Highly Destabilizing	0.959	D	0.62	neutral	N	0.492121796	None	None	N
L/T	0.861	likely_pathogenic	0.8343	pathogenic	-1.988	Destabilizing	0.939	D	0.577	neutral	None	None	None	None	N
L/V	0.2662	likely_benign	0.2304	benign	-1.281	Destabilizing	0.134	N	0.191	neutral	N	0.488398813	None	None	N
L/W	0.9314	likely_pathogenic	0.9078	pathogenic	-1.525	Destabilizing	0.999	D	0.643	neutral	N	0.5196338	None	None	N
L/Y	0.9599	likely_pathogenic	0.9448	pathogenic	-1.262	Destabilizing	0.964	D	0.713	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.