TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6008	18247;18248;18249	chr2:178730511;178730510;178730509	chr2:179595238;179595237;179595236
N2AB	5691	17296;17297;17298	chr2:178730511;178730510;178730509	chr2:179595238;179595237;179595236
N2A	4764	14515;14516;14517	chr2:178730511;178730510;178730509	chr2:179595238;179595237;179595236
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-43
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.3123
• 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/A	None	None	0.543	D	0.475	0.662	0.684920834152	gnomAD-4.0.0	1.38598E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81741E-06	0	0
V/I	None	None	0.987	N	0.588	0.469	0.725759869084	gnomAD-4.0.0	1.63982E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.95409E-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
V/A	0.8865	likely_pathogenic	0.8942	pathogenic	-1.708	Destabilizing	0.543	D	0.475	neutral	D	0.614339371	None	None	N
V/C	0.9859	likely_pathogenic	0.9869	pathogenic	-1.709	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.9982	pathogenic	-2.029	Highly Destabilizing	0.998	D	0.721	prob.delet.	D	0.652323293	None	None	N
V/E	0.9888	likely_pathogenic	0.9904	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/F	0.9351	likely_pathogenic	0.9436	pathogenic	-1.427	Destabilizing	0.999	D	0.691	prob.neutral	D	0.65171788	None	None	N
V/G	0.9588	likely_pathogenic	0.9656	pathogenic	-2.02	Highly Destabilizing	0.997	D	0.693	prob.neutral	D	0.652323293	None	None	N
V/H	0.9982	likely_pathogenic	0.9985	pathogenic	-1.412	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/I	0.0974	likely_benign	0.0998	benign	-0.928	Destabilizing	0.987	D	0.588	neutral	N	0.51875292	None	None	N
V/K	0.9942	likely_pathogenic	0.9954	pathogenic	-1.318	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
V/L	0.7668	likely_pathogenic	0.7576	pathogenic	-0.928	Destabilizing	0.973	D	0.581	neutral	D	0.617428951	None	None	N
V/M	0.7834	likely_pathogenic	0.7794	pathogenic	-0.978	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/N	0.9891	likely_pathogenic	0.9908	pathogenic	-1.316	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
V/P	0.9858	likely_pathogenic	0.9894	pathogenic	-1.158	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
V/Q	0.9897	likely_pathogenic	0.9916	pathogenic	-1.523	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/R	0.989	likely_pathogenic	0.9914	pathogenic	-0.828	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
V/S	0.96	likely_pathogenic	0.9667	pathogenic	-1.871	Destabilizing	0.995	D	0.652	neutral	None	None	None	None	N
V/T	0.8974	likely_pathogenic	0.9078	pathogenic	-1.734	Destabilizing	0.992	D	0.649	neutral	None	None	None	None	N
V/W	0.9987	likely_pathogenic	0.9989	pathogenic	-1.573	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
V/Y	0.995	likely_pathogenic	0.9957	pathogenic	-1.26	Destabilizing	1.0	D	0.695	prob.neutral	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.