TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27894	83905;83906;83907	chr2:178562452;178562451;178562450	chr2:179427179;179427178;179427177
N2AB	26253	78982;78983;78984	chr2:178562452;178562451;178562450	chr2:179427179;179427178;179427177
N2A	25326	76201;76202;76203	chr2:178562452;178562451;178562450	chr2:179427179;179427178;179427177
N2B	18829	56710;56711;56712	chr2:178562452;178562451;178562450	chr2:179427179;179427178;179427177
Novex-1	18954	57085;57086;57087	chr2:178562452;178562451;178562450	chr2:179427179;179427178;179427177
Novex-2	19021	57286;57287;57288	chr2:178562452;178562451;178562450	chr2:179427179;179427178;179427177
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: Fn3-91
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7356
• 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/Q	rs753572520	0.41	0.983	N	0.664	0.286	0.253726318573	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66113E-04
K/Q	rs753572520	0.41	0.983	N	0.664	0.286	0.253726318573	gnomAD-4.0.0	1.59252E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	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	0.6867	likely_pathogenic	0.7962	pathogenic	-0.002	Destabilizing	0.916	D	0.588	neutral	None	None	None	None	N
K/C	0.8446	likely_pathogenic	0.892	pathogenic	-0.116	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.9179	likely_pathogenic	0.9564	pathogenic	0.136	Stabilizing	0.987	D	0.595	neutral	None	None	None	None	N
K/E	0.6462	likely_pathogenic	0.7919	pathogenic	0.142	Stabilizing	0.892	D	0.553	neutral	N	0.465260392	None	None	N
K/F	0.9305	likely_pathogenic	0.9558	pathogenic	-0.218	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
K/G	0.7988	likely_pathogenic	0.8798	pathogenic	-0.207	Destabilizing	0.975	D	0.543	neutral	None	None	None	None	N
K/H	0.5151	ambiguous	0.5995	pathogenic	-0.523	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
K/I	0.6516	likely_pathogenic	0.7435	pathogenic	0.457	Stabilizing	0.983	D	0.668	neutral	N	0.471648727	None	None	N
K/L	0.663	likely_pathogenic	0.7539	pathogenic	0.457	Stabilizing	0.975	D	0.541	neutral	None	None	None	None	N
K/M	0.5735	likely_pathogenic	0.6891	pathogenic	0.315	Stabilizing	0.999	D	0.613	neutral	None	None	None	None	N
K/N	0.8411	likely_pathogenic	0.9094	pathogenic	0.323	Stabilizing	0.983	D	0.655	neutral	N	0.466773655	None	None	N
K/P	0.7383	likely_pathogenic	0.8237	pathogenic	0.333	Stabilizing	0.033	N	0.469	neutral	None	None	None	None	N
K/Q	0.3363	likely_benign	0.4439	ambiguous	0.13	Stabilizing	0.983	D	0.664	neutral	N	0.515729285	None	None	N
K/R	0.0695	likely_benign	0.0687	benign	0.022	Stabilizing	0.944	D	0.529	neutral	N	0.438847369	None	None	N
K/S	0.8281	likely_pathogenic	0.903	pathogenic	-0.191	Destabilizing	0.916	D	0.577	neutral	None	None	None	None	N
K/T	0.5845	likely_pathogenic	0.7163	pathogenic	-0.033	Destabilizing	0.967	D	0.581	neutral	N	0.502626702	None	None	N
K/V	0.5903	likely_pathogenic	0.6914	pathogenic	0.333	Stabilizing	0.987	D	0.605	neutral	None	None	None	None	N
K/W	0.8818	likely_pathogenic	0.9109	pathogenic	-0.217	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.8315	likely_pathogenic	0.8815	pathogenic	0.142	Stabilizing	0.996	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.