TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32632	98119;98120;98121	chr2:178540272;178540271;178540270	chr2:179404999;179404998;179404997
N2AB	30991	93196;93197;93198	chr2:178540272;178540271;178540270	chr2:179404999;179404998;179404997
N2A	30064	90415;90416;90417	chr2:178540272;178540271;178540270	chr2:179404999;179404998;179404997
N2B	23567	70924;70925;70926	chr2:178540272;178540271;178540270	chr2:179404999;179404998;179404997
Novex-1	23692	71299;71300;71301	chr2:178540272;178540271;178540270	chr2:179404999;179404998;179404997
Novex-2	23759	71500;71501;71502	chr2:178540272;178540271;178540270	chr2:179404999;179404998;179404997
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-126
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3427
• 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
V/L	None	None	0.948	N	0.489	0.263	0.468420198123	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	None	0	0	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
V/A	0.8222	likely_pathogenic	0.8237	pathogenic	-1.807	Destabilizing	0.994	D	0.594	neutral	N	0.518174944	None	None	I
V/C	0.9427	likely_pathogenic	0.9346	pathogenic	-1.335	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
V/D	0.9738	likely_pathogenic	0.9739	pathogenic	-1.716	Destabilizing	0.999	D	0.843	deleterious	N	0.468952929	None	None	I
V/E	0.9385	likely_pathogenic	0.9382	pathogenic	-1.693	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
V/F	0.8013	likely_pathogenic	0.7984	pathogenic	-1.405	Destabilizing	0.998	D	0.827	deleterious	N	0.501260645	None	None	I
V/G	0.868	likely_pathogenic	0.861	pathogenic	-2.166	Highly Destabilizing	0.999	D	0.823	deleterious	D	0.52224219	None	None	I
V/H	0.9889	likely_pathogenic	0.9874	pathogenic	-1.603	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
V/I	0.0853	likely_benign	0.0784	benign	-0.903	Destabilizing	0.543	D	0.257	neutral	N	0.385258027	None	None	I
V/K	0.9698	likely_pathogenic	0.9678	pathogenic	-1.504	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/L	0.5112	ambiguous	0.4623	ambiguous	-0.903	Destabilizing	0.948	D	0.489	neutral	N	0.499567754	None	None	I
V/M	0.6002	likely_pathogenic	0.5695	pathogenic	-0.665	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	I
V/N	0.9341	likely_pathogenic	0.9238	pathogenic	-1.346	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
V/P	0.7385	likely_pathogenic	0.7351	pathogenic	-1.17	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/Q	0.9637	likely_pathogenic	0.9607	pathogenic	-1.51	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
V/R	0.9632	likely_pathogenic	0.9612	pathogenic	-0.923	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
V/S	0.9266	likely_pathogenic	0.9199	pathogenic	-1.93	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
V/T	0.8217	likely_pathogenic	0.8048	pathogenic	-1.788	Destabilizing	0.996	D	0.736	prob.delet.	None	None	None	None	I
V/W	0.9906	likely_pathogenic	0.9902	pathogenic	-1.588	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
V/Y	0.9638	likely_pathogenic	0.9634	pathogenic	-1.323	Destabilizing	1.0	D	0.825	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.