TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25702	77329;77330;77331	chr2:178569028;178569027;178569026	chr2:179433755;179433754;179433753
N2AB	24061	72406;72407;72408	chr2:178569028;178569027;178569026	chr2:179433755;179433754;179433753
N2A	23134	69625;69626;69627	chr2:178569028;178569027;178569026	chr2:179433755;179433754;179433753
N2B	16637	50134;50135;50136	chr2:178569028;178569027;178569026	chr2:179433755;179433754;179433753
Novex-1	16762	50509;50510;50511	chr2:178569028;178569027;178569026	chr2:179433755;179433754;179433753
Novex-2	16829	50710;50711;50712	chr2:178569028;178569027;178569026	chr2:179433755;179433754;179433753
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-75
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1006
• 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
P/R	None	None	1.0	D	0.929	0.76	0.736097903372	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.727	likely_pathogenic	0.6637	pathogenic	-2.466	Highly Destabilizing	0.998	D	0.817	deleterious	D	0.528673513	None	None	N
P/C	0.9679	likely_pathogenic	0.9552	pathogenic	-2.152	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
P/D	0.9995	likely_pathogenic	0.9994	pathogenic	-3.31	Highly Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.9974	pathogenic	-3.031	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/F	0.999	likely_pathogenic	0.9984	pathogenic	-1.16	Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
P/G	0.9942	likely_pathogenic	0.9926	pathogenic	-3.002	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/H	0.9984	likely_pathogenic	0.9976	pathogenic	-2.627	Highly Destabilizing	1.0	D	0.927	deleterious	D	0.571985594	None	None	N
P/I	0.8442	likely_pathogenic	0.7772	pathogenic	-0.911	Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	N
P/K	0.9991	likely_pathogenic	0.9987	pathogenic	-1.794	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/L	0.8955	likely_pathogenic	0.8494	pathogenic	-0.911	Destabilizing	0.999	D	0.883	deleterious	D	0.558690277	None	None	N
P/M	0.982	likely_pathogenic	0.9719	pathogenic	-1.423	Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
P/N	0.9992	likely_pathogenic	0.9988	pathogenic	-2.37	Highly Destabilizing	0.999	D	0.923	deleterious	None	None	None	None	N
P/Q	0.9967	likely_pathogenic	0.9951	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/R	0.9967	likely_pathogenic	0.9954	pathogenic	-1.799	Destabilizing	1.0	D	0.929	deleterious	D	0.544980569	None	None	N
P/S	0.9807	likely_pathogenic	0.9731	pathogenic	-2.871	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.54210696	None	None	N
P/T	0.925	likely_pathogenic	0.887	pathogenic	-2.454	Highly Destabilizing	0.998	D	0.833	deleterious	D	0.54447359	None	None	N
P/V	0.6472	likely_pathogenic	0.5535	ambiguous	-1.412	Destabilizing	0.995	D	0.859	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.639	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9995	pathogenic	-1.426	Destabilizing	1.0	D	0.941	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.