TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22818	68677;68678;68679	chr2:178578063;178578062;178578061	chr2:179442790;179442789;179442788
N2AB	21177	63754;63755;63756	chr2:178578063;178578062;178578061	chr2:179442790;179442789;179442788
N2A	20250	60973;60974;60975	chr2:178578063;178578062;178578061	chr2:179442790;179442789;179442788
N2B	13753	41482;41483;41484	chr2:178578063;178578062;178578061	chr2:179442790;179442789;179442788
Novex-1	13878	41857;41858;41859	chr2:178578063;178578062;178578061	chr2:179442790;179442789;179442788
Novex-2	13945	42058;42059;42060	chr2:178578063;178578062;178578061	chr2:179442790;179442789;179442788
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: Fn3-53
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0991
• 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	0.767	N	0.348	0.418	0.655682557923	gnomAD-4.0.0	1.5925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05
V/L	None	None	0.981	N	0.635	0.565	0.81868435926	gnomAD-4.0.0	1.5925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86041E-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	0.6548	likely_pathogenic	0.5846	pathogenic	-2.385	Highly Destabilizing	0.998	D	0.673	neutral	D	0.55363153	None	None	N
V/C	0.918	likely_pathogenic	0.8945	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
V/D	0.9963	likely_pathogenic	0.9964	pathogenic	-3.364	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.651307143	None	None	N
V/E	0.9892	likely_pathogenic	0.9892	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/F	0.9097	likely_pathogenic	0.8865	pathogenic	-1.172	Destabilizing	0.999	D	0.78	deleterious	D	0.560214896	None	None	N
V/G	0.8378	likely_pathogenic	0.8125	pathogenic	-2.94	Highly Destabilizing	1.0	D	0.856	deleterious	D	0.651307143	None	None	N
V/H	0.9975	likely_pathogenic	0.997	pathogenic	-2.791	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/I	0.1211	likely_benign	0.1067	benign	-0.767	Destabilizing	0.767	D	0.348	neutral	N	0.501348865	None	None	N
V/K	0.9945	likely_pathogenic	0.9947	pathogenic	-1.923	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/L	0.6419	likely_pathogenic	0.5221	ambiguous	-0.767	Destabilizing	0.981	D	0.635	neutral	N	0.519127633	None	None	N
V/M	0.7134	likely_pathogenic	0.6032	pathogenic	-1.179	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/N	0.9797	likely_pathogenic	0.9774	pathogenic	-2.524	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/P	0.9915	likely_pathogenic	0.9923	pathogenic	-1.29	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/Q	0.9884	likely_pathogenic	0.9872	pathogenic	-2.195	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/R	0.9887	likely_pathogenic	0.9898	pathogenic	-1.954	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/S	0.8976	likely_pathogenic	0.8691	pathogenic	-3.006	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/T	0.7505	likely_pathogenic	0.6792	pathogenic	-2.579	Highly Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9984	pathogenic	-1.784	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/Y	0.9909	likely_pathogenic	0.9896	pathogenic	-1.531	Destabilizing	1.0	D	0.782	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.