TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25675	77248;77249;77250	chr2:178569109;178569108;178569107	chr2:179433836;179433835;179433834
N2AB	24034	72325;72326;72327	chr2:178569109;178569108;178569107	chr2:179433836;179433835;179433834
N2A	23107	69544;69545;69546	chr2:178569109;178569108;178569107	chr2:179433836;179433835;179433834
N2B	16610	50053;50054;50055	chr2:178569109;178569108;178569107	chr2:179433836;179433835;179433834
Novex-1	16735	50428;50429;50430	chr2:178569109;178569108;178569107	chr2:179433836;179433835;179433834
Novex-2	16802	50629;50630;50631	chr2:178569109;178569108;178569107	chr2:179433836;179433835;179433834
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: Fn3-74
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0828
• 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	0.18	D	0.314	0.243	0.582797214371	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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	0.9233	likely_pathogenic	0.9355	pathogenic	-2.483	Highly Destabilizing	0.994	D	0.65	neutral	D	0.564494083	None	None	N
V/C	0.9771	likely_pathogenic	0.9802	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/D	0.9994	likely_pathogenic	0.9994	pathogenic	-3.554	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.657343424	None	None	N
V/E	0.9978	likely_pathogenic	0.9978	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/F	0.9386	likely_pathogenic	0.9539	pathogenic	-1.37	Destabilizing	0.999	D	0.828	deleterious	D	0.587371278	None	None	N
V/G	0.9735	likely_pathogenic	0.9749	pathogenic	-3.041	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.657343424	None	None	N
V/H	0.9993	likely_pathogenic	0.9994	pathogenic	-2.89	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.0981	likely_benign	0.1068	benign	-0.852	Destabilizing	0.18	N	0.314	neutral	D	0.533121046	None	None	N
V/K	0.9982	likely_pathogenic	0.9982	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/L	0.7573	likely_pathogenic	0.8034	pathogenic	-0.852	Destabilizing	0.849	D	0.595	neutral	D	0.542333996	None	None	N
V/M	0.8321	likely_pathogenic	0.8623	pathogenic	-1.136	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
V/N	0.9968	likely_pathogenic	0.9969	pathogenic	-2.762	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/P	0.998	likely_pathogenic	0.9981	pathogenic	-1.379	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/Q	0.9974	likely_pathogenic	0.9975	pathogenic	-2.459	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/R	0.9967	likely_pathogenic	0.9968	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
V/S	0.9867	likely_pathogenic	0.9878	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/T	0.9568	likely_pathogenic	0.9622	pathogenic	-2.814	Highly Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9995	pathogenic	-1.985	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Y	0.9959	likely_pathogenic	0.9966	pathogenic	-1.7	Destabilizing	1.0	D	0.842	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.