TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33623	101092;101093;101094	chr2:178535748;178535747;178535746	chr2:179400475;179400474;179400473
N2AB	31982	96169;96170;96171	chr2:178535748;178535747;178535746	chr2:179400475;179400474;179400473
N2A	31055	93388;93389;93390	chr2:178535748;178535747;178535746	chr2:179400475;179400474;179400473
N2B	24558	73897;73898;73899	chr2:178535748;178535747;178535746	chr2:179400475;179400474;179400473
Novex-1	24683	74272;74273;74274	chr2:178535748;178535747;178535746	chr2:179400475;179400474;179400473
Novex-2	24750	74473;74474;74475	chr2:178535748;178535747;178535746	chr2:179400475;179400474;179400473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-159
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.2289
• 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	rs1199682198	-0.368	1.0	D	0.757	0.735	0.856589233873	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/L	rs1199682198	-0.368	1.0	D	0.757	0.735	0.856589233873	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85842E-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	0.9806	likely_pathogenic	0.9739	pathogenic	-1.063	Destabilizing	1.0	D	0.713	prob.delet.	D	0.538249527	None	None	N
P/C	0.999	likely_pathogenic	0.9989	pathogenic	-0.597	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/D	0.9955	likely_pathogenic	0.9949	pathogenic	-0.759	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/E	0.9958	likely_pathogenic	0.9933	pathogenic	-0.81	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
P/F	0.9994	likely_pathogenic	0.9992	pathogenic	-0.982	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/G	0.9903	likely_pathogenic	0.9903	pathogenic	-1.299	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
P/H	0.9966	likely_pathogenic	0.9957	pathogenic	-0.827	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/I	0.9944	likely_pathogenic	0.9915	pathogenic	-0.548	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/K	0.997	likely_pathogenic	0.9955	pathogenic	-0.834	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/L	0.9895	likely_pathogenic	0.9849	pathogenic	-0.548	Destabilizing	1.0	D	0.757	deleterious	D	0.572078276	None	None	N
P/M	0.9965	likely_pathogenic	0.9954	pathogenic	-0.439	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
P/N	0.9956	likely_pathogenic	0.9946	pathogenic	-0.527	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
P/Q	0.9959	likely_pathogenic	0.9941	pathogenic	-0.735	Destabilizing	1.0	D	0.772	deleterious	D	0.531666161	None	None	N
P/R	0.9938	likely_pathogenic	0.9898	pathogenic	-0.295	Destabilizing	1.0	D	0.791	deleterious	D	0.603945554	None	None	N
P/S	0.9951	likely_pathogenic	0.9942	pathogenic	-0.951	Destabilizing	1.0	D	0.739	prob.delet.	D	0.549263437	None	None	N
P/T	0.9838	likely_pathogenic	0.9796	pathogenic	-0.899	Destabilizing	1.0	D	0.733	prob.delet.	D	0.587694028	None	None	N
P/V	0.9875	likely_pathogenic	0.9812	pathogenic	-0.684	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9994	pathogenic	-1.115	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/Y	0.9989	likely_pathogenic	0.9983	pathogenic	-0.829	Destabilizing	1.0	D	0.825	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.