TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25379	76360;76361;76362	chr2:178569997;178569996;178569995	chr2:179434724;179434723;179434722
N2AB	23738	71437;71438;71439	chr2:178569997;178569996;178569995	chr2:179434724;179434723;179434722
N2A	22811	68656;68657;68658	chr2:178569997;178569996;178569995	chr2:179434724;179434723;179434722
N2B	16314	49165;49166;49167	chr2:178569997;178569996;178569995	chr2:179434724;179434723;179434722
Novex-1	16439	49540;49541;49542	chr2:178569997;178569996;178569995	chr2:179434724;179434723;179434722
Novex-2	16506	49741;49742;49743	chr2:178569997;178569996;178569995	chr2:179434724;179434723;179434722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-72
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0766
• 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	None	None	0.997	N	0.657	0.414	0.774835214283	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7331	likely_pathogenic	0.5847	pathogenic	-2.608	Highly Destabilizing	0.999	D	0.688	prob.neutral	D	0.554454451	None	None	N
V/C	0.9405	likely_pathogenic	0.9299	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.9973	pathogenic	-3.198	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.652467966	None	None	N
V/E	0.9956	likely_pathogenic	0.9926	pathogenic	-2.916	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/F	0.9408	likely_pathogenic	0.9116	pathogenic	-1.18	Destabilizing	1.0	D	0.833	deleterious	D	0.583915011	None	None	N
V/G	0.9297	likely_pathogenic	0.8726	pathogenic	-3.124	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.652467966	None	None	N
V/H	0.9987	likely_pathogenic	0.998	pathogenic	-2.694	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/I	0.1101	likely_benign	0.1157	benign	-1.094	Destabilizing	0.997	D	0.657	neutral	N	0.493448826	None	None	N
V/K	0.9976	likely_pathogenic	0.9964	pathogenic	-1.828	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/L	0.7127	likely_pathogenic	0.6652	pathogenic	-1.094	Destabilizing	0.997	D	0.716	prob.delet.	N	0.508429664	None	None	N
V/M	0.8372	likely_pathogenic	0.7927	pathogenic	-1.567	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/N	0.9929	likely_pathogenic	0.9884	pathogenic	-2.398	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/P	0.9959	likely_pathogenic	0.994	pathogenic	-1.585	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/Q	0.9947	likely_pathogenic	0.9913	pathogenic	-2.075	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/R	0.9936	likely_pathogenic	0.9901	pathogenic	-1.866	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/S	0.9509	likely_pathogenic	0.9132	pathogenic	-2.872	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/T	0.8971	likely_pathogenic	0.8559	pathogenic	-2.458	Highly Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9987	pathogenic	-1.598	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/Y	0.9944	likely_pathogenic	0.9917	pathogenic	-1.474	Destabilizing	1.0	D	0.822	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.