TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15718	47377;47378;47379	chr2:178618306;178618305;178618304	chr2:179483033;179483032;179483031
N2AB	14077	42454;42455;42456	chr2:178618306;178618305;178618304	chr2:179483033;179483032;179483031
N2A	13150	39673;39674;39675	chr2:178618306;178618305;178618304	chr2:179483033;179483032;179483031
N2B	6653	20182;20183;20184	chr2:178618306;178618305;178618304	chr2:179483033;179483032;179483031
Novex-1	6778	20557;20558;20559	chr2:178618306;178618305;178618304	chr2:179483033;179483032;179483031
Novex-2	6845	20758;20759;20760	chr2:178618306;178618305;178618304	chr2:179483033;179483032;179483031
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: Fn3-1
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1225
• 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	0.987	N	0.554	0.193	0.542587012665	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86223E-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	0.7183	likely_pathogenic	0.7349	pathogenic	-1.511	Destabilizing	0.973	D	0.669	neutral	N	0.512334522	None	None	N
V/C	0.9568	likely_pathogenic	0.9498	pathogenic	-1.149	Destabilizing	0.46	N	0.578	neutral	None	None	None	None	N
V/D	0.9947	likely_pathogenic	0.9945	pathogenic	-2.009	Highly Destabilizing	0.999	D	0.844	deleterious	D	0.575307426	None	None	N
V/E	0.9796	likely_pathogenic	0.9804	pathogenic	-1.723	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/F	0.8217	likely_pathogenic	0.8199	pathogenic	-0.782	Destabilizing	0.999	D	0.767	deleterious	D	0.610178995	None	None	N
V/G	0.9399	likely_pathogenic	0.9369	pathogenic	-2.108	Highly Destabilizing	0.998	D	0.837	deleterious	D	0.742693797	None	None	N
V/H	0.9955	likely_pathogenic	0.9952	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/I	0.1185	likely_benign	0.1315	benign	0.177	Stabilizing	0.987	D	0.554	neutral	N	0.474965271	None	None	N
V/K	0.9884	likely_pathogenic	0.9881	pathogenic	-1.071	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/L	0.6021	likely_pathogenic	0.6349	pathogenic	0.177	Stabilizing	0.973	D	0.684	prob.neutral	N	0.491314575	None	None	N
V/M	0.6046	likely_pathogenic	0.6453	pathogenic	-0.111	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
V/N	0.9863	likely_pathogenic	0.9844	pathogenic	-1.574	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/P	0.9887	likely_pathogenic	0.9869	pathogenic	-0.359	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Q	0.9805	likely_pathogenic	0.9799	pathogenic	-1.249	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/R	0.9822	likely_pathogenic	0.9805	pathogenic	-1.307	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/S	0.9455	likely_pathogenic	0.941	pathogenic	-2.206	Highly Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
V/T	0.8461	likely_pathogenic	0.8495	pathogenic	-1.743	Destabilizing	0.996	D	0.658	neutral	None	None	None	None	N
V/W	0.9977	likely_pathogenic	0.9977	pathogenic	-1.313	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/Y	0.9854	likely_pathogenic	0.9849	pathogenic	-0.833	Destabilizing	1.0	D	0.758	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.