TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32736	98431;98432;98433	chr2:178539859;178539858;178539857	chr2:179404586;179404585;179404584
N2AB	31095	93508;93509;93510	chr2:178539859;178539858;178539857	chr2:179404586;179404585;179404584
N2A	30168	90727;90728;90729	chr2:178539859;178539858;178539857	chr2:179404586;179404585;179404584
N2B	23671	71236;71237;71238	chr2:178539859;178539858;178539857	chr2:179404586;179404585;179404584
Novex-1	23796	71611;71612;71613	chr2:178539859;178539858;178539857	chr2:179404586;179404585;179404584
Novex-2	23863	71812;71813;71814	chr2:178539859;178539858;178539857	chr2:179404586;179404585;179404584
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-155
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.281
• 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
C/Y	rs1693533292	None	0.999	N	0.863	0.384	0.807158024866	gnomAD-4.0.0	3.18246E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85837E-06	1.43275E-05	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
C/A	0.5236	ambiguous	0.4598	ambiguous	-1.958	Destabilizing	0.964	D	0.661	neutral	None	None	None	None	I
C/D	0.9922	likely_pathogenic	0.9854	pathogenic	-0.691	Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	I
C/E	0.9909	likely_pathogenic	0.9843	pathogenic	-0.529	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	I
C/F	0.7433	likely_pathogenic	0.6887	pathogenic	-1.178	Destabilizing	0.999	D	0.861	deleterious	N	0.46689048	None	None	I
C/G	0.4665	ambiguous	0.3967	ambiguous	-2.305	Highly Destabilizing	0.997	D	0.841	deleterious	N	0.508334458	None	None	I
C/H	0.9636	likely_pathogenic	0.9379	pathogenic	-2.125	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
C/I	0.6896	likely_pathogenic	0.6364	pathogenic	-1.034	Destabilizing	0.996	D	0.79	deleterious	None	None	None	None	I
C/K	0.9924	likely_pathogenic	0.9864	pathogenic	-1.221	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	I
C/L	0.7569	likely_pathogenic	0.7249	pathogenic	-1.034	Destabilizing	0.985	D	0.711	prob.delet.	None	None	None	None	I
C/M	0.863	likely_pathogenic	0.8282	pathogenic	0.152	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
C/N	0.9509	likely_pathogenic	0.9205	pathogenic	-1.468	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	I
C/P	0.9192	likely_pathogenic	0.8813	pathogenic	-1.318	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	I
C/Q	0.9636	likely_pathogenic	0.941	pathogenic	-1.211	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	I
C/R	0.9548	likely_pathogenic	0.9333	pathogenic	-1.167	Destabilizing	0.997	D	0.871	deleterious	D	0.527189578	None	None	I
C/S	0.5402	ambiguous	0.4529	ambiguous	-2.006	Highly Destabilizing	0.961	D	0.727	prob.delet.	N	0.478800985	None	None	I
C/T	0.6824	likely_pathogenic	0.6068	pathogenic	-1.646	Destabilizing	0.469	N	0.495	neutral	None	None	None	None	I
C/V	0.5147	ambiguous	0.4778	ambiguous	-1.318	Destabilizing	0.985	D	0.727	prob.delet.	None	None	None	None	I
C/W	0.9455	likely_pathogenic	0.9198	pathogenic	-1.227	Destabilizing	1.0	D	0.858	deleterious	N	0.508334458	None	None	I
C/Y	0.8711	likely_pathogenic	0.82	pathogenic	-1.225	Destabilizing	0.999	D	0.863	deleterious	N	0.470989578	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.