TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14736	44431;44432;44433	chr2:178630316;178630315;178630314	chr2:179495043;179495042;179495041
N2AB	13095	39508;39509;39510	chr2:178630316;178630315;178630314	chr2:179495043;179495042;179495041
N2A	12168	36727;36728;36729	chr2:178630316;178630315;178630314	chr2:179495043;179495042;179495041
N2B	5671	17236;17237;17238	chr2:178630316;178630315;178630314	chr2:179495043;179495042;179495041
Novex-1	5796	17611;17612;17613	chr2:178630316;178630315;178630314	chr2:179495043;179495042;179495041
Novex-2	5863	17812;17813;17814	chr2:178630316;178630315;178630314	chr2:179495043;179495042;179495041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-98
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0786
• 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/S	None	None	0.791	N	0.646	0.237	0.41859458845	gnomAD-4.0.0	1.59311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86103E-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	0.7273	likely_pathogenic	0.7878	pathogenic	-0.577	Destabilizing	0.182	N	0.46	neutral	None	None	None	None	N
C/D	0.9949	likely_pathogenic	0.996	pathogenic	-1.656	Destabilizing	0.982	D	0.789	deleterious	None	None	None	None	N
C/E	0.9969	likely_pathogenic	0.9979	pathogenic	-1.536	Destabilizing	0.946	D	0.773	deleterious	None	None	None	None	N
C/F	0.8331	likely_pathogenic	0.8787	pathogenic	-0.63	Destabilizing	0.868	D	0.766	deleterious	N	0.465612694	None	None	N
C/G	0.7022	likely_pathogenic	0.7232	pathogenic	-0.812	Destabilizing	0.791	D	0.739	deleterious	N	0.431672887	None	None	N
C/H	0.988	likely_pathogenic	0.991	pathogenic	-1.453	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
C/I	0.5388	ambiguous	0.6624	pathogenic	-0.017	Destabilizing	0.338	N	0.588	neutral	None	None	None	None	N
C/K	0.9975	likely_pathogenic	0.9983	pathogenic	-0.494	Destabilizing	0.946	D	0.775	deleterious	None	None	None	None	N
C/L	0.512	ambiguous	0.5868	pathogenic	-0.017	Destabilizing	0.338	N	0.562	neutral	None	None	None	None	N
C/M	0.8485	likely_pathogenic	0.9052	pathogenic	0.309	Stabilizing	0.946	D	0.748	deleterious	None	None	None	None	N
C/N	0.9674	likely_pathogenic	0.9728	pathogenic	-0.878	Destabilizing	0.982	D	0.831	deleterious	None	None	None	None	N
C/P	0.9792	likely_pathogenic	0.987	pathogenic	-0.177	Destabilizing	0.982	D	0.801	deleterious	None	None	None	None	N
C/Q	0.9905	likely_pathogenic	0.9935	pathogenic	-0.79	Destabilizing	0.982	D	0.823	deleterious	None	None	None	None	N
C/R	0.9788	likely_pathogenic	0.9819	pathogenic	-0.711	Destabilizing	0.93	D	0.833	deleterious	N	0.46671967	None	None	N
C/S	0.7828	likely_pathogenic	0.7988	pathogenic	-0.936	Destabilizing	0.791	D	0.646	neutral	N	0.41511583	None	None	N
C/T	0.7121	likely_pathogenic	0.7169	pathogenic	-0.683	Destabilizing	0.712	D	0.647	neutral	None	None	None	None	N
C/V	0.3444	ambiguous	0.4593	ambiguous	-0.177	Destabilizing	0.001	N	0.282	neutral	None	None	None	None	N
C/W	0.978	likely_pathogenic	0.9852	pathogenic	-1.117	Destabilizing	0.993	D	0.749	deleterious	N	0.468210823	None	None	N
C/Y	0.9466	likely_pathogenic	0.9629	pathogenic	-0.686	Destabilizing	0.93	D	0.794	deleterious	N	0.46671967	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.