TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26084	78475;78476;78477	chr2:178567882;178567881;178567880	chr2:179432609;179432608;179432607
N2AB	24443	73552;73553;73554	chr2:178567882;178567881;178567880	chr2:179432609;179432608;179432607
N2A	23516	70771;70772;70773	chr2:178567882;178567881;178567880	chr2:179432609;179432608;179432607
N2B	17019	51280;51281;51282	chr2:178567882;178567881;178567880	chr2:179432609;179432608;179432607
Novex-1	17144	51655;51656;51657	chr2:178567882;178567881;178567880	chr2:179432609;179432608;179432607
Novex-2	17211	51856;51857;51858	chr2:178567882;178567881;178567880	chr2:179432609;179432608;179432607
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-77
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.1627
• 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	rs1252241115	None	0.002	N	0.23	0.143	0.392547445146	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs1252241115	None	0.002	N	0.23	0.143	0.392547445146	gnomAD-4.0.0	6.57497E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47089E-05	0	0
V/I	None	None	0.002	N	0.171	0.084	0.320256813643	gnomAD-4.0.0	3.18356E-06	None	None	None	None	N	None	0	0	None	0	5.54631E-05	None	0	0	0	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	0.1728	likely_benign	0.2328	benign	-1.351	Destabilizing	0.002	N	0.23	neutral	N	0.495447226	None	None	N
V/C	0.6909	likely_pathogenic	0.7612	pathogenic	-0.928	Destabilizing	0.012	N	0.491	neutral	None	None	None	None	N
V/D	0.6323	likely_pathogenic	0.7305	pathogenic	-0.95	Destabilizing	0.842	D	0.739	deleterious	None	None	None	None	N
V/E	0.4983	ambiguous	0.5831	pathogenic	-0.96	Destabilizing	0.664	D	0.614	neutral	N	0.511859474	None	None	N
V/F	0.1994	likely_benign	0.2141	benign	-1.025	Destabilizing	0.005	N	0.443	neutral	None	None	None	None	N
V/G	0.3353	likely_benign	0.4373	ambiguous	-1.656	Destabilizing	0.22	N	0.695	prob.delet.	N	0.505104851	None	None	N
V/H	0.6971	likely_pathogenic	0.7595	pathogenic	-1.083	Destabilizing	0.984	D	0.701	prob.delet.	None	None	None	None	N
V/I	0.0736	likely_benign	0.0763	benign	-0.624	Destabilizing	0.002	N	0.171	neutral	N	0.485056875	None	None	N
V/K	0.5571	ambiguous	0.6519	pathogenic	-1.104	Destabilizing	0.724	D	0.617	neutral	None	None	None	None	N
V/L	0.1837	likely_benign	0.239	benign	-0.624	Destabilizing	0.039	N	0.471	neutral	N	0.500332971	None	None	N
V/M	0.1472	likely_benign	0.1764	benign	-0.492	Destabilizing	0.724	D	0.439	neutral	None	None	None	None	N
V/N	0.3992	ambiguous	0.5094	ambiguous	-0.893	Destabilizing	0.842	D	0.713	prob.delet.	None	None	None	None	N
V/P	0.4952	ambiguous	0.5983	pathogenic	-0.831	Destabilizing	0.842	D	0.643	neutral	None	None	None	None	N
V/Q	0.4624	ambiguous	0.5415	ambiguous	-1.064	Destabilizing	0.842	D	0.619	neutral	None	None	None	None	N
V/R	0.474	ambiguous	0.5694	pathogenic	-0.559	Destabilizing	0.724	D	0.717	prob.delet.	None	None	None	None	N
V/S	0.2588	likely_benign	0.3393	benign	-1.445	Destabilizing	0.272	N	0.576	neutral	None	None	None	None	N
V/T	0.1539	likely_benign	0.1765	benign	-1.341	Destabilizing	0.428	N	0.483	neutral	None	None	None	None	N
V/W	0.8471	likely_pathogenic	0.8775	pathogenic	-1.175	Destabilizing	0.984	D	0.733	deleterious	None	None	None	None	N
V/Y	0.6037	likely_pathogenic	0.6604	pathogenic	-0.892	Destabilizing	0.568	D	0.516	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.