TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3431	10516;10517;10518	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721
N2AB	3431	10516;10517;10518	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721
N2A	3431	10516;10517;10518	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721
N2B	3385	10378;10379;10380	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721
Novex-1	3385	10378;10379;10380	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721
Novex-2	3385	10378;10379;10380	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721
Novex-3	3431	10516;10517;10518	chr2:178758996;178758995;178758994	chr2:179623723;179623722;179623721

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-24
• Domain position: 87
• Structural Position: 174
• Q(SASA): 0.0924
• 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	0.895	0.879	0.939559954431	gnomAD-4.0.0	1.59082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02261E-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	0.9366	likely_pathogenic	0.9563	pathogenic	-2.661	Highly Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
L/C	0.9098	likely_pathogenic	0.926	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/D	0.9987	likely_pathogenic	0.9992	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/E	0.9933	likely_pathogenic	0.9951	pathogenic	-2.707	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/F	0.5879	likely_pathogenic	0.6521	pathogenic	-1.64	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/G	0.9874	likely_pathogenic	0.9905	pathogenic	-3.222	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/H	0.9763	likely_pathogenic	0.9774	pathogenic	-2.655	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/I	0.1682	likely_benign	0.213	benign	-1.026	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
L/K	0.9838	likely_pathogenic	0.9887	pathogenic	-1.9	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/M	0.4	ambiguous	0.4639	ambiguous	-1.127	Destabilizing	1.0	D	0.808	deleterious	D	0.723344648	None	None	N
L/N	0.9926	likely_pathogenic	0.9948	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/P	0.9951	likely_pathogenic	0.996	pathogenic	-1.554	Destabilizing	1.0	D	0.895	deleterious	D	0.802833583	None	None	N
L/Q	0.9694	likely_pathogenic	0.9765	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.91	deleterious	D	0.802833583	None	None	N
L/R	0.9595	likely_pathogenic	0.97	pathogenic	-1.663	Destabilizing	1.0	D	0.908	deleterious	D	0.802833583	None	None	N
L/S	0.9896	likely_pathogenic	0.9933	pathogenic	-3.042	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/T	0.9483	likely_pathogenic	0.9696	pathogenic	-2.65	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/V	0.217	likely_benign	0.2926	benign	-1.554	Destabilizing	0.999	D	0.602	neutral	D	0.613009359	None	None	N
L/W	0.9558	likely_pathogenic	0.961	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/Y	0.9598	likely_pathogenic	0.9666	pathogenic	-1.739	Destabilizing	1.0	D	0.885	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.