TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7194	21805;21806;21807	chr2:178723520;178723519;178723518	chr2:179588247;179588246;179588245
N2AB	6877	20854;20855;20856	chr2:178723520;178723519;178723518	chr2:179588247;179588246;179588245
N2A	5950	18073;18074;18075	chr2:178723520;178723519;178723518	chr2:179588247;179588246;179588245
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-56
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0442
• 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	0.991	D	0.922	0.807	0.914077616967	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4339E-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	0.8409	likely_pathogenic	0.8184	pathogenic	-2.765	Highly Destabilizing	0.769	D	0.751	deleterious	None	None	None	None	N
L/C	0.8936	likely_pathogenic	0.8736	pathogenic	-2.083	Highly Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9985	pathogenic	-3.634	Highly Destabilizing	0.979	D	0.919	deleterious	None	None	None	None	N
L/E	0.9883	likely_pathogenic	0.9858	pathogenic	-3.317	Highly Destabilizing	0.979	D	0.899	deleterious	None	None	None	None	N
L/F	0.6419	likely_pathogenic	0.5864	pathogenic	-1.739	Destabilizing	0.959	D	0.773	deleterious	None	None	None	None	N
L/G	0.9697	likely_pathogenic	0.9625	pathogenic	-3.352	Highly Destabilizing	0.979	D	0.908	deleterious	None	None	None	None	N
L/H	0.9839	likely_pathogenic	0.9809	pathogenic	-3.083	Highly Destabilizing	0.998	D	0.913	deleterious	None	None	None	None	N
L/I	0.3058	likely_benign	0.2949	benign	-0.988	Destabilizing	0.769	D	0.671	neutral	None	None	None	None	N
L/K	0.9827	likely_pathogenic	0.9795	pathogenic	-2.273	Highly Destabilizing	0.959	D	0.895	deleterious	None	None	None	None	N
L/M	0.2136	likely_benign	0.2041	benign	-1.168	Destabilizing	0.135	N	0.383	neutral	D	0.545741037	None	None	N
L/N	0.9925	likely_pathogenic	0.9907	pathogenic	-3.006	Highly Destabilizing	0.979	D	0.919	deleterious	None	None	None	None	N
L/P	0.9956	likely_pathogenic	0.9945	pathogenic	-1.573	Destabilizing	0.991	D	0.922	deleterious	D	0.579355881	None	None	N
L/Q	0.9636	likely_pathogenic	0.9594	pathogenic	-2.66	Highly Destabilizing	0.946	D	0.903	deleterious	D	0.579355881	None	None	N
L/R	0.9673	likely_pathogenic	0.962	pathogenic	-2.325	Highly Destabilizing	0.946	D	0.903	deleterious	D	0.579355881	None	None	N
L/S	0.9846	likely_pathogenic	0.9829	pathogenic	-3.518	Highly Destabilizing	0.959	D	0.892	deleterious	None	None	None	None	N
L/T	0.9334	likely_pathogenic	0.9296	pathogenic	-3.039	Highly Destabilizing	0.959	D	0.817	deleterious	None	None	None	None	N
L/V	0.3235	likely_benign	0.3281	benign	-1.573	Destabilizing	0.716	D	0.687	prob.neutral	D	0.543347954	None	None	N
L/W	0.926	likely_pathogenic	0.9149	pathogenic	-2.158	Highly Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
L/Y	0.9465	likely_pathogenic	0.936	pathogenic	-1.949	Destabilizing	0.979	D	0.835	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.