TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4945	15058;15059;15060	chr2:178735613;178735612;178735611	chr2:179600340;179600339;179600338
N2AB	4628	14107;14108;14109	chr2:178735613;178735612;178735611	chr2:179600340;179600339;179600338
N2A	3701	11326;11327;11328	chr2:178735613;178735612;178735611	chr2:179600340;179600339;179600338
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-32
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0735
• 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/P	None	None	1.0	D	0.919	0.832	0.861823502751	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	0	None	0	0	0	0	0
L/V	None	None	0.767	N	0.42	0.387	0.688782367926	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.5528	ambiguous	0.6177	pathogenic	-2.715	Highly Destabilizing	0.997	D	0.745	deleterious	None	None	None	None	N
L/C	0.6508	likely_pathogenic	0.7099	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/D	0.9976	likely_pathogenic	0.9984	pathogenic	-3.648	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
L/E	0.977	likely_pathogenic	0.9834	pathogenic	-3.341	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/F	0.2092	likely_benign	0.2164	benign	-1.725	Destabilizing	0.999	D	0.787	deleterious	N	0.413505311	None	None	N
L/G	0.931	likely_pathogenic	0.95	pathogenic	-3.281	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/H	0.9299	likely_pathogenic	0.9465	pathogenic	-3.051	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.580176002	None	None	N
L/I	0.0947	likely_benign	0.0946	benign	-1.002	Destabilizing	0.992	D	0.655	neutral	N	0.517730751	None	None	N
L/K	0.9677	likely_pathogenic	0.9779	pathogenic	-2.291	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/M	0.1203	likely_benign	0.1393	benign	-1.229	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/N	0.9825	likely_pathogenic	0.988	pathogenic	-3.011	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/P	0.9881	likely_pathogenic	0.9923	pathogenic	-1.567	Destabilizing	1.0	D	0.919	deleterious	D	0.622534494	None	None	N
L/Q	0.9007	likely_pathogenic	0.9249	pathogenic	-2.677	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/R	0.9227	likely_pathogenic	0.9423	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.923	deleterious	D	0.622534494	None	None	N
L/S	0.9036	likely_pathogenic	0.9315	pathogenic	-3.491	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/T	0.7204	likely_pathogenic	0.787	pathogenic	-3.028	Highly Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
L/V	0.0899	likely_benign	0.0935	benign	-1.567	Destabilizing	0.767	D	0.42	neutral	N	0.518154053	None	None	N
L/W	0.7135	likely_pathogenic	0.7473	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/Y	0.8003	likely_pathogenic	0.8156	pathogenic	-1.946	Destabilizing	1.0	D	0.841	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.