TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24456	73591;73592;73593	chr2:178572766;178572765;178572764	chr2:179437493;179437492;179437491
N2AB	22815	68668;68669;68670	chr2:178572766;178572765;178572764	chr2:179437493;179437492;179437491
N2A	21888	65887;65888;65889	chr2:178572766;178572765;178572764	chr2:179437493;179437492;179437491
N2B	15391	46396;46397;46398	chr2:178572766;178572765;178572764	chr2:179437493;179437492;179437491
Novex-1	15516	46771;46772;46773	chr2:178572766;178572765;178572764	chr2:179437493;179437492;179437491
Novex-2	15583	46972;46973;46974	chr2:178572766;178572765;178572764	chr2:179437493;179437492;179437491
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: Ig-132
• Domain position: 26
• Structural Position: 42
• Q(SASA): 0.5839
• Predicted PPI site: I

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/H	None	None	1.0	D	0.761	0.69	0.868472475781	gnomAD-4.0.0	1.59187E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85951E-06	0	0
P/R	None	None	1.0	D	0.76	0.698	0.86712314379	gnomAD-4.0.0	1.59187E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85951E-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	0.9602	likely_pathogenic	0.9541	pathogenic	-0.446	Destabilizing	1.0	D	0.728	prob.delet.	D	0.557999623	None	None	I
P/C	0.9972	likely_pathogenic	0.9968	pathogenic	-0.575	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/D	0.9925	likely_pathogenic	0.9908	pathogenic	-0.267	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/E	0.9917	likely_pathogenic	0.9892	pathogenic	-0.399	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
P/F	0.9981	likely_pathogenic	0.998	pathogenic	-0.801	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/G	0.9902	likely_pathogenic	0.9889	pathogenic	-0.55	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/H	0.991	likely_pathogenic	0.99	pathogenic	-0.191	Destabilizing	1.0	D	0.761	deleterious	D	0.631976756	None	None	I
P/I	0.9849	likely_pathogenic	0.9826	pathogenic	-0.332	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/K	0.992	likely_pathogenic	0.991	pathogenic	-0.333	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
P/L	0.9522	likely_pathogenic	0.9441	pathogenic	-0.332	Destabilizing	1.0	D	0.738	prob.delet.	D	0.615957395	None	None	I
P/M	0.9888	likely_pathogenic	0.9874	pathogenic	-0.288	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/N	0.9913	likely_pathogenic	0.991	pathogenic	-0.06	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/Q	0.9903	likely_pathogenic	0.989	pathogenic	-0.34	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/R	0.9858	likely_pathogenic	0.9843	pathogenic	0.185	Stabilizing	1.0	D	0.76	deleterious	D	0.631573148	None	None	I
P/S	0.9885	likely_pathogenic	0.987	pathogenic	-0.402	Destabilizing	1.0	D	0.735	prob.delet.	D	0.56884895	None	None	I
P/T	0.9689	likely_pathogenic	0.9633	pathogenic	-0.438	Destabilizing	1.0	D	0.731	prob.delet.	D	0.631573148	None	None	I
P/V	0.9726	likely_pathogenic	0.968	pathogenic	-0.336	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
P/W	0.9991	likely_pathogenic	0.9989	pathogenic	-0.863	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/Y	0.9973	likely_pathogenic	0.9972	pathogenic	-0.552	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I

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.