TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3111	9556;9557;9558	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624
N2AB	3111	9556;9557;9558	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624
N2A	3111	9556;9557;9558	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624
N2B	3065	9418;9419;9420	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624
Novex-1	3065	9418;9419;9420	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624
Novex-2	3065	9418;9419;9420	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624
Novex-3	3111	9556;9557;9558	chr2:178767899;178767898;178767897	chr2:179632626;179632625;179632624

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-21
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.1637
• 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
V/I	rs2090778418	None	0.987	N	0.523	0.202	0.639788913552	gnomAD-4.0.0	3.18123E-06	None	None	None	None	N	None	0	0	None	0	5.55124E-05	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	0.4882	ambiguous	0.5276	ambiguous	-1.972	Destabilizing	0.543	D	0.307	neutral	D	0.529276012	None	None	N
V/C	0.8681	likely_pathogenic	0.8877	pathogenic	-1.215	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/D	0.8918	likely_pathogenic	0.8944	pathogenic	-2.66	Highly Destabilizing	0.999	D	0.819	deleterious	D	0.551109715	None	None	N
V/E	0.7427	likely_pathogenic	0.7307	pathogenic	-2.608	Highly Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
V/F	0.3984	ambiguous	0.4137	ambiguous	-1.357	Destabilizing	0.999	D	0.841	deleterious	N	0.506294339	None	None	N
V/G	0.5919	likely_pathogenic	0.6543	pathogenic	-2.326	Highly Destabilizing	0.997	D	0.734	prob.delet.	N	0.503538588	None	None	N
V/H	0.8407	likely_pathogenic	0.8288	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/I	0.0793	likely_benign	0.0799	benign	-1.039	Destabilizing	0.987	D	0.523	neutral	N	0.507105914	None	None	N
V/K	0.6901	likely_pathogenic	0.6617	pathogenic	-1.731	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/L	0.3171	likely_benign	0.335	benign	-1.039	Destabilizing	0.973	D	0.484	neutral	N	0.499302261	None	None	N
V/M	0.2463	likely_benign	0.2754	benign	-0.732	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
V/N	0.6333	likely_pathogenic	0.6678	pathogenic	-1.628	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/P	0.9917	likely_pathogenic	0.9899	pathogenic	-1.324	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/Q	0.596	likely_pathogenic	0.5899	pathogenic	-1.744	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/R	0.624	likely_pathogenic	0.5941	pathogenic	-1.215	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/S	0.5173	ambiguous	0.5735	pathogenic	-2.032	Highly Destabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	N
V/T	0.3658	ambiguous	0.3934	ambiguous	-1.896	Destabilizing	0.992	D	0.518	neutral	None	None	None	None	N
V/W	0.9558	likely_pathogenic	0.9536	pathogenic	-1.739	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
V/Y	0.8274	likely_pathogenic	0.8365	pathogenic	-1.503	Destabilizing	1.0	D	0.841	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.