TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21267	64024;64025;64026	chr2:178587412;178587411;178587410	chr2:179452139;179452138;179452137
N2AB	19626	59101;59102;59103	chr2:178587412;178587411;178587410	chr2:179452139;179452138;179452137
N2A	18699	56320;56321;56322	chr2:178587412;178587411;178587410	chr2:179452139;179452138;179452137
N2B	12202	36829;36830;36831	chr2:178587412;178587411;178587410	chr2:179452139;179452138;179452137
Novex-1	12327	37204;37205;37206	chr2:178587412;178587411;178587410	chr2:179452139;179452138;179452137
Novex-2	12394	37405;37406;37407	chr2:178587412;178587411;178587410	chr2:179452139;179452138;179452137
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: Fn3-42
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1289
• 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/L	rs200365508	-0.396	0.986	D	0.791	0.652	None	gnomAD-2.1.1	1.11E-05	None	None	None	None	N	None	1.28899E-04	0	None	0	0	None	0	None	0	0	0
P/L	rs200365508	-0.396	0.986	D	0.791	0.652	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.17339E-04	0	0	0	0	None	0	0	0	0	0
P/L	rs200365508	-0.396	0.986	D	0.791	0.652	None	gnomAD-4.0.0	8.70561E-06	None	None	None	None	N	None	1.87326E-04	0	None	0	0	None	0	0	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
P/A	0.8372	likely_pathogenic	0.8988	pathogenic	-1.09	Destabilizing	0.952	D	0.701	prob.delet.	D	0.62423491	None	None	N
P/C	0.9874	likely_pathogenic	0.9927	pathogenic	-1.989	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/D	0.9995	likely_pathogenic	0.9997	pathogenic	-3.316	Highly Destabilizing	0.989	D	0.751	deleterious	None	None	None	None	N
P/E	0.9988	likely_pathogenic	0.9993	pathogenic	-3.267	Highly Destabilizing	0.989	D	0.752	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9998	pathogenic	-0.86	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
P/G	0.9935	likely_pathogenic	0.9962	pathogenic	-1.353	Destabilizing	0.989	D	0.757	deleterious	None	None	None	None	N
P/H	0.9983	likely_pathogenic	0.999	pathogenic	-0.813	Destabilizing	0.246	N	0.54	neutral	D	0.666397795	None	None	N
P/I	0.9928	likely_pathogenic	0.9957	pathogenic	-0.435	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9996	pathogenic	-1.289	Destabilizing	0.989	D	0.755	deleterious	None	None	None	None	N
P/L	0.9753	likely_pathogenic	0.9851	pathogenic	-0.435	Destabilizing	0.986	D	0.791	deleterious	D	0.634157269	None	None	N
P/M	0.9958	likely_pathogenic	0.9976	pathogenic	-0.867	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/N	0.9992	likely_pathogenic	0.9995	pathogenic	-1.712	Destabilizing	0.989	D	0.811	deleterious	None	None	None	None	N
P/Q	0.9977	likely_pathogenic	0.9987	pathogenic	-1.903	Destabilizing	0.989	D	0.836	deleterious	None	None	None	None	N
P/R	0.9964	likely_pathogenic	0.9978	pathogenic	-0.86	Destabilizing	0.986	D	0.811	deleterious	D	0.65017663	None	None	N
P/S	0.9756	likely_pathogenic	0.9862	pathogenic	-1.902	Destabilizing	0.986	D	0.741	deleterious	D	0.649974826	None	None	N
P/T	0.973	likely_pathogenic	0.9841	pathogenic	-1.761	Destabilizing	0.993	D	0.749	deleterious	D	0.666195991	None	None	N
P/V	0.9707	likely_pathogenic	0.9823	pathogenic	-0.627	Destabilizing	0.995	D	0.8	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.193	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9998	pathogenic	-0.795	Destabilizing	0.989	D	0.799	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.