TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30554	91885;91886;91887	chr2:178550178;178550177;178550176	chr2:179414905;179414904;179414903
N2AB	28913	86962;86963;86964	chr2:178550178;178550177;178550176	chr2:179414905;179414904;179414903
N2A	27986	84181;84182;84183	chr2:178550178;178550177;178550176	chr2:179414905;179414904;179414903
N2B	21489	64690;64691;64692	chr2:178550178;178550177;178550176	chr2:179414905;179414904;179414903
Novex-1	21614	65065;65066;65067	chr2:178550178;178550177;178550176	chr2:179414905;179414904;179414903
Novex-2	21681	65266;65267;65268	chr2:178550178;178550177;178550176	chr2:179414905;179414904;179414903
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-149
• Domain position: 23
• Structural Position: 42
• Q(SASA): 0.5331
• 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/L	rs1698777400	None	1.0	D	0.739	0.73	0.882422999392	gnomAD-4.0.0	1.43684E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.88892E-05	0	0
P/Q	None	None	1.0	D	0.726	0.751	0.794492043152	gnomAD-4.0.0	6.84211E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99486E-07	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	0.9111	likely_pathogenic	0.9013	pathogenic	-0.455	Destabilizing	1.0	D	0.712	prob.delet.	D	0.570837186	None	None	I
P/C	0.9921	likely_pathogenic	0.9907	pathogenic	-0.577	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/D	0.9898	likely_pathogenic	0.989	pathogenic	-0.388	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
P/E	0.9863	likely_pathogenic	0.9828	pathogenic	-0.512	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
P/F	0.9964	likely_pathogenic	0.9953	pathogenic	-0.749	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/G	0.9764	likely_pathogenic	0.973	pathogenic	-0.571	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
P/H	0.9816	likely_pathogenic	0.9779	pathogenic	-0.182	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
P/I	0.9743	likely_pathogenic	0.9695	pathogenic	-0.302	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/K	0.9891	likely_pathogenic	0.9858	pathogenic	-0.447	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
P/L	0.9429	likely_pathogenic	0.93	pathogenic	-0.302	Destabilizing	1.0	D	0.739	prob.delet.	D	0.61270709	None	None	I
P/M	0.9778	likely_pathogenic	0.9725	pathogenic	-0.343	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/N	0.9848	likely_pathogenic	0.983	pathogenic	-0.148	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
P/Q	0.9779	likely_pathogenic	0.9723	pathogenic	-0.412	Destabilizing	1.0	D	0.726	prob.delet.	D	0.564089236	None	None	I
P/R	0.9743	likely_pathogenic	0.968	pathogenic	0.089	Stabilizing	1.0	D	0.766	deleterious	D	0.64968199	None	None	I
P/S	0.9729	likely_pathogenic	0.9701	pathogenic	-0.473	Destabilizing	1.0	D	0.721	prob.delet.	D	0.570330207	None	None	I
P/T	0.9406	likely_pathogenic	0.9322	pathogenic	-0.501	Destabilizing	1.0	D	0.714	prob.delet.	D	0.64968199	None	None	I
P/V	0.9512	likely_pathogenic	0.9443	pathogenic	-0.319	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/W	0.9982	likely_pathogenic	0.9978	pathogenic	-0.826	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
P/Y	0.9945	likely_pathogenic	0.993	pathogenic	-0.53	Destabilizing	1.0	D	0.786	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.