TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8690	26293;26294;26295	chr2:178715118;178715117;178715116	chr2:179579845;179579844;179579843
N2AB	8373	25342;25343;25344	chr2:178715118;178715117;178715116	chr2:179579845;179579844;179579843
N2A	7446	22561;22562;22563	chr2:178715118;178715117;178715116	chr2:179579845;179579844;179579843
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-72
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.5868
• 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/E	rs1060500411	0.24	0.991	N	0.492	0.384	0.397391247328	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
K/E	rs1060500411	0.24	0.991	N	0.492	0.384	0.397391247328	gnomAD-4.0.0	3.18278E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.76464E-05	0	0	0	0
K/R	rs755911258	-0.419	0.34	N	0.256	0.098	0.235038932564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/R	rs755911258	-0.419	0.34	N	0.256	0.098	0.235038932564	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79904E-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
K/A	0.8989	likely_pathogenic	0.8876	pathogenic	-0.799	Destabilizing	0.998	D	0.491	neutral	None	None	None	None	N
K/C	0.9465	likely_pathogenic	0.94	pathogenic	-0.778	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/D	0.9526	likely_pathogenic	0.9535	pathogenic	-0.332	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
K/E	0.7328	likely_pathogenic	0.7021	pathogenic	-0.185	Destabilizing	0.991	D	0.492	neutral	N	0.506681019	None	None	N
K/F	0.9749	likely_pathogenic	0.9665	pathogenic	-0.37	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/G	0.936	likely_pathogenic	0.9342	pathogenic	-1.208	Destabilizing	0.615	D	0.313	neutral	None	None	None	None	N
K/H	0.6033	likely_pathogenic	0.5944	pathogenic	-1.543	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
K/I	0.8123	likely_pathogenic	0.7504	pathogenic	0.284	Stabilizing	0.997	D	0.665	neutral	None	None	None	None	N
K/L	0.7999	likely_pathogenic	0.7557	pathogenic	0.284	Stabilizing	0.991	D	0.489	neutral	None	None	None	None	N
K/M	0.681	likely_pathogenic	0.6413	pathogenic	0.214	Stabilizing	1.0	D	0.594	neutral	N	0.506536197	None	None	N
K/N	0.9017	likely_pathogenic	0.8909	pathogenic	-0.714	Destabilizing	1.0	D	0.481	neutral	N	0.512068196	None	None	N
K/P	0.9875	likely_pathogenic	0.989	pathogenic	-0.047	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/Q	0.4029	ambiguous	0.3946	ambiguous	-0.732	Destabilizing	0.994	D	0.516	neutral	N	0.503622072	None	None	N
K/R	0.1083	likely_benign	0.107	benign	-0.791	Destabilizing	0.34	N	0.256	neutral	N	0.474992675	None	None	N
K/S	0.9047	likely_pathogenic	0.8974	pathogenic	-1.415	Destabilizing	0.998	D	0.484	neutral	None	None	None	None	N
K/T	0.6723	likely_pathogenic	0.6508	pathogenic	-1.041	Destabilizing	0.999	D	0.519	neutral	N	0.508798605	None	None	N
K/V	0.7751	likely_pathogenic	0.7233	pathogenic	-0.047	Destabilizing	0.993	D	0.602	neutral	None	None	None	None	N
K/W	0.9489	likely_pathogenic	0.9433	pathogenic	-0.228	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
K/Y	0.9156	likely_pathogenic	0.9044	pathogenic	0.062	Stabilizing	0.998	D	0.645	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.