TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20141	60646;60647;60648	chr2:178591304;178591303;178591302	chr2:179456031;179456030;179456029
N2AB	18500	55723;55724;55725	chr2:178591304;178591303;178591302	chr2:179456031;179456030;179456029
N2A	17573	52942;52943;52944	chr2:178591304;178591303;178591302	chr2:179456031;179456030;179456029
N2B	11076	33451;33452;33453	chr2:178591304;178591303;178591302	chr2:179456031;179456030;179456029
Novex-1	11201	33826;33827;33828	chr2:178591304;178591303;178591302	chr2:179456031;179456030;179456029
Novex-2	11268	34027;34028;34029	chr2:178591304;178591303;178591302	chr2:179456031;179456030;179456029
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-120
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0879
• 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
C/R	None	None	1.0	N	0.795	0.677	0.885774903276	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79938E-06	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
C/A	0.4679	ambiguous	0.5038	ambiguous	-1.09	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	N
C/D	0.9926	likely_pathogenic	0.9935	pathogenic	-1.735	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
C/E	0.9968	likely_pathogenic	0.997	pathogenic	-1.584	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
C/F	0.91	likely_pathogenic	0.9276	pathogenic	-0.951	Destabilizing	1.0	D	0.793	deleterious	D	0.527381579	None	None	N
C/G	0.509	ambiguous	0.5591	ambiguous	-1.377	Destabilizing	1.0	D	0.761	deleterious	N	0.488161545	None	None	N
C/H	0.9862	likely_pathogenic	0.9879	pathogenic	-1.94	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
C/I	0.7076	likely_pathogenic	0.7451	pathogenic	-0.368	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
C/K	0.9979	likely_pathogenic	0.998	pathogenic	-0.893	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
C/L	0.7398	likely_pathogenic	0.7694	pathogenic	-0.368	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
C/M	0.9	likely_pathogenic	0.9104	pathogenic	0.27	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
C/N	0.9486	likely_pathogenic	0.9527	pathogenic	-1.335	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
C/P	0.9518	likely_pathogenic	0.9603	pathogenic	-0.583	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
C/Q	0.9894	likely_pathogenic	0.9902	pathogenic	-1.146	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
C/R	0.9831	likely_pathogenic	0.9844	pathogenic	-1.116	Destabilizing	1.0	D	0.795	deleterious	N	0.5062658	None	None	N
C/S	0.4325	ambiguous	0.4661	ambiguous	-1.497	Destabilizing	1.0	D	0.746	deleterious	N	0.448555436	None	None	N
C/T	0.4967	ambiguous	0.5343	ambiguous	-1.187	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
C/V	0.5065	ambiguous	0.5288	ambiguous	-0.583	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
C/W	0.9904	likely_pathogenic	0.9925	pathogenic	-1.385	Destabilizing	1.0	D	0.753	deleterious	N	0.50651929	None	None	N
C/Y	0.9725	likely_pathogenic	0.9773	pathogenic	-1.052	Destabilizing	1.0	D	0.797	deleterious	N	0.5062658	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.