TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35455	106588;106589;106590	chr2:178530252;178530251;178530250	chr2:179394979;179394978;179394977
N2AB	33814	101665;101666;101667	chr2:178530252;178530251;178530250	chr2:179394979;179394978;179394977
N2A	32887	98884;98885;98886	chr2:178530252;178530251;178530250	chr2:179394979;179394978;179394977
N2B	26390	79393;79394;79395	chr2:178530252;178530251;178530250	chr2:179394979;179394978;179394977
Novex-1	26515	79768;79769;79770	chr2:178530252;178530251;178530250	chr2:179394979;179394978;179394977
Novex-2	26582	79969;79970;79971	chr2:178530252;178530251;178530250	chr2:179394979;179394978;179394977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-166
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.0737
• 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
K/N	rs757588041	-1.091	0.999	N	0.715	0.411	0.144782658237	gnomAD-2.1.1	8.32E-06	None	None	None	None	N	None	0	0	None	0	1.14626E-04	None	0	None	0	0	0
K/N	rs757588041	-1.091	0.999	N	0.715	0.411	0.144782658237	gnomAD-4.0.0	3.26314E-06	None	None	None	None	N	None	0	0	None	0	5.57724E-05	None	0	0	0	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
K/A	0.8042	likely_pathogenic	0.808	pathogenic	-1.296	Destabilizing	0.998	D	0.584	neutral	None	None	None	None	N
K/C	0.9447	likely_pathogenic	0.9357	pathogenic	-1.397	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
K/D	0.9704	likely_pathogenic	0.9743	pathogenic	-1.078	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
K/E	0.6049	likely_pathogenic	0.6123	pathogenic	-0.855	Destabilizing	0.997	D	0.501	neutral	N	0.509699981	None	None	N
K/F	0.9594	likely_pathogenic	0.9542	pathogenic	-0.938	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
K/G	0.9058	likely_pathogenic	0.9082	pathogenic	-1.744	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
K/H	0.7407	likely_pathogenic	0.7283	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/I	0.7122	likely_pathogenic	0.7034	pathogenic	-0.067	Destabilizing	0.999	D	0.862	deleterious	N	0.501849168	None	None	N
K/L	0.7635	likely_pathogenic	0.7367	pathogenic	-0.067	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
K/M	0.5545	ambiguous	0.5367	ambiguous	-0.145	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/N	0.888	likely_pathogenic	0.8905	pathogenic	-1.334	Destabilizing	0.999	D	0.715	prob.delet.	N	0.491342236	None	None	N
K/P	0.9897	likely_pathogenic	0.9907	pathogenic	-0.451	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
K/Q	0.4467	ambiguous	0.4333	ambiguous	-1.197	Destabilizing	0.999	D	0.689	prob.neutral	N	0.490835257	None	None	N
K/R	0.1203	likely_benign	0.1145	benign	-0.978	Destabilizing	0.997	D	0.503	neutral	N	0.452384309	None	None	N
K/S	0.8848	likely_pathogenic	0.8935	pathogenic	-2.033	Highly Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
K/T	0.7026	likely_pathogenic	0.7306	pathogenic	-1.55	Destabilizing	0.999	D	0.761	deleterious	N	0.509193002	None	None	N
K/V	0.6723	likely_pathogenic	0.6722	pathogenic	-0.451	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
K/W	0.9599	likely_pathogenic	0.9589	pathogenic	-0.849	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
K/Y	0.9096	likely_pathogenic	0.9014	pathogenic	-0.504	Destabilizing	0.999	D	0.867	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.