TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25721	77386;77387;77388	chr2:178568971;178568970;178568969	chr2:179433698;179433697;179433696
N2AB	24080	72463;72464;72465	chr2:178568971;178568970;178568969	chr2:179433698;179433697;179433696
N2A	23153	69682;69683;69684	chr2:178568971;178568970;178568969	chr2:179433698;179433697;179433696
N2B	16656	50191;50192;50193	chr2:178568971;178568970;178568969	chr2:179433698;179433697;179433696
Novex-1	16781	50566;50567;50568	chr2:178568971;178568970;178568969	chr2:179433698;179433697;179433696
Novex-2	16848	50767;50768;50769	chr2:178568971;178568970;178568969	chr2:179433698;179433697;179433696
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: Fn3-75
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5792
• 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	None	None	0.998	N	0.727	0.398	0.278968121808	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7714	likely_pathogenic	0.8271	pathogenic	-0.173	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
K/C	0.9299	likely_pathogenic	0.9569	pathogenic	-0.44	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
K/D	0.9731	likely_pathogenic	0.9792	pathogenic	0.022	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/E	0.7921	likely_pathogenic	0.827	pathogenic	0.088	Stabilizing	0.997	D	0.631	neutral	N	0.51109147	None	None	N
K/F	0.9676	likely_pathogenic	0.9785	pathogenic	-0.204	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/G	0.9102	likely_pathogenic	0.938	pathogenic	-0.432	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/H	0.7348	likely_pathogenic	0.7946	pathogenic	-0.625	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/I	0.7721	likely_pathogenic	0.8466	pathogenic	0.455	Stabilizing	0.992	D	0.816	deleterious	N	0.505437701	None	None	N
K/L	0.7156	likely_pathogenic	0.7869	pathogenic	0.455	Stabilizing	0.994	D	0.763	deleterious	None	None	None	None	N
K/M	0.6693	likely_pathogenic	0.7425	pathogenic	0.044	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/N	0.9388	likely_pathogenic	0.951	pathogenic	-0.092	Destabilizing	1.0	D	0.745	deleterious	N	0.50594468	None	None	N
K/P	0.6923	likely_pathogenic	0.6951	pathogenic	0.274	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/Q	0.4486	ambiguous	0.5379	ambiguous	-0.128	Destabilizing	0.998	D	0.727	prob.delet.	N	0.46948268	None	None	N
K/R	0.0996	likely_benign	0.1199	benign	-0.167	Destabilizing	0.996	D	0.609	neutral	N	0.518345516	None	None	N
K/S	0.8983	likely_pathogenic	0.9218	pathogenic	-0.589	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
K/T	0.7455	likely_pathogenic	0.8051	pathogenic	-0.341	Destabilizing	0.999	D	0.795	deleterious	N	0.470950711	None	None	N
K/V	0.6884	likely_pathogenic	0.78	pathogenic	0.274	Stabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
K/W	0.9667	likely_pathogenic	0.9786	pathogenic	-0.224	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/Y	0.928	likely_pathogenic	0.9479	pathogenic	0.117	Stabilizing	0.999	D	0.813	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.