TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2201	6826;6827;6828	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835
N2AB	2201	6826;6827;6828	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835
N2A	2201	6826;6827;6828	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835
N2B	2155	6688;6689;6690	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835
Novex-1	2155	6688;6689;6690	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835
Novex-2	2155	6688;6689;6690	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835
Novex-3	2201	6826;6827;6828	chr2:178775110;178775109;178775108	chr2:179639837;179639836;179639835

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-11
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.3905
• 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/S	rs763426070	-1.095	1.0	N	0.793	0.418	0.119812018005	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.53E-05	None	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	0.2548	likely_benign	0.2925	benign	-1.115	Destabilizing	1.0	D	0.735	prob.delet.	N	0.340960968	None	None	N
P/C	0.9474	likely_pathogenic	0.9558	pathogenic	-0.786	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
P/D	0.8952	likely_pathogenic	0.9142	pathogenic	-0.602	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/E	0.8338	likely_pathogenic	0.8599	pathogenic	-0.633	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/F	0.9289	likely_pathogenic	0.9412	pathogenic	-0.903	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/G	0.7861	likely_pathogenic	0.8198	pathogenic	-1.377	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
P/H	0.7142	likely_pathogenic	0.7457	pathogenic	-0.773	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
P/I	0.7906	likely_pathogenic	0.8311	pathogenic	-0.524	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
P/K	0.9007	likely_pathogenic	0.9177	pathogenic	-0.868	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/L	0.4533	ambiguous	0.5009	ambiguous	-0.524	Destabilizing	1.0	D	0.746	deleterious	D	0.532895108	None	None	N
P/M	0.7753	likely_pathogenic	0.8143	pathogenic	-0.484	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
P/N	0.791	likely_pathogenic	0.8246	pathogenic	-0.648	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/Q	0.652	likely_pathogenic	0.6978	pathogenic	-0.82	Destabilizing	1.0	D	0.789	deleterious	N	0.461285783	None	None	N
P/R	0.7568	likely_pathogenic	0.7851	pathogenic	-0.335	Destabilizing	1.0	D	0.765	deleterious	N	0.461517121	None	None	N
P/S	0.481	ambiguous	0.5304	ambiguous	-1.158	Destabilizing	1.0	D	0.793	deleterious	N	0.389362171	None	None	N
P/T	0.4433	ambiguous	0.5001	ambiguous	-1.075	Destabilizing	1.0	D	0.789	deleterious	N	0.430478974	None	None	N
P/V	0.6522	likely_pathogenic	0.7036	pathogenic	-0.685	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/W	0.967	likely_pathogenic	0.9723	pathogenic	-1.02	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
P/Y	0.8901	likely_pathogenic	0.9049	pathogenic	-0.737	Destabilizing	1.0	D	0.762	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.