TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4835	14728;14729;14730	chr2:178735943;178735942;178735941	chr2:179600670;179600669;179600668
N2AB	4518	13777;13778;13779	chr2:178735943;178735942;178735941	chr2:179600670;179600669;179600668
N2A	3591	10996;10997;10998	chr2:178735943;178735942;178735941	chr2:179600670;179600669;179600668
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-31
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2012
• 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/R	None	None	0.896	D	0.549	0.615	0.8332244366	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.5071	ambiguous	0.4593	ambiguous	-2.065	Highly Destabilizing	0.25	N	0.441	neutral	None	None	None	None	N
L/C	0.6804	likely_pathogenic	0.6437	pathogenic	-1.395	Destabilizing	0.977	D	0.504	neutral	None	None	None	None	N
L/D	0.9345	likely_pathogenic	0.9232	pathogenic	-1.61	Destabilizing	0.005	N	0.41	neutral	None	None	None	None	N
L/E	0.7455	likely_pathogenic	0.706	pathogenic	-1.404	Destabilizing	0.447	N	0.551	neutral	None	None	None	None	N
L/F	0.1947	likely_benign	0.1726	benign	-1.233	Destabilizing	0.81	D	0.501	neutral	D	0.60952903	None	None	N
L/G	0.8168	likely_pathogenic	0.7789	pathogenic	-2.55	Highly Destabilizing	0.766	D	0.535	neutral	None	None	None	None	N
L/H	0.5732	likely_pathogenic	0.5355	ambiguous	-1.732	Destabilizing	0.99	D	0.567	neutral	D	0.753109507	None	None	N
L/I	0.0757	likely_benign	0.0728	benign	-0.688	Destabilizing	0.001	N	0.1	neutral	N	0.47291378	None	None	N
L/K	0.622	likely_pathogenic	0.5775	pathogenic	-1.385	Destabilizing	0.92	D	0.519	neutral	None	None	None	None	N
L/M	0.1913	likely_benign	0.1684	benign	-0.717	Destabilizing	0.85	D	0.539	neutral	None	None	None	None	N
L/N	0.7723	likely_pathogenic	0.7369	pathogenic	-1.67	Destabilizing	0.85	D	0.563	neutral	None	None	None	None	N
L/P	0.6462	likely_pathogenic	0.5954	pathogenic	-1.126	Destabilizing	0.963	D	0.573	neutral	D	0.638081705	None	None	N
L/Q	0.4784	ambiguous	0.4284	ambiguous	-1.509	Destabilizing	0.92	D	0.554	neutral	None	None	None	None	N
L/R	0.4815	ambiguous	0.4331	ambiguous	-1.217	Destabilizing	0.896	D	0.549	neutral	D	0.71572492	None	None	N
L/S	0.6547	likely_pathogenic	0.616	pathogenic	-2.415	Highly Destabilizing	0.617	D	0.494	neutral	None	None	None	None	N
L/T	0.5208	ambiguous	0.487	ambiguous	-2.047	Highly Destabilizing	0.617	D	0.455	neutral	None	None	None	None	N
L/V	0.1017	likely_benign	0.0934	benign	-1.126	Destabilizing	0.002	N	0.15	neutral	N	0.521089063	None	None	N
L/W	0.5114	ambiguous	0.4748	ambiguous	-1.406	Destabilizing	0.992	D	0.546	neutral	None	None	None	None	N
L/Y	0.5718	likely_pathogenic	0.5211	ambiguous	-1.133	Destabilizing	0.92	D	0.542	neutral	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.