TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7561	22906;22907;22908	chr2:178721982;178721981;178721980	chr2:179586709;179586708;179586707
N2AB	7244	21955;21956;21957	chr2:178721982;178721981;178721980	chr2:179586709;179586708;179586707
N2A	6317	19174;19175;19176	chr2:178721982;178721981;178721980	chr2:179586709;179586708;179586707
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-60
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1771
• 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
Y/C	rs786205544	None	1.0	N	0.792	0.505	0.754199488981	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
Y/C	rs786205544	None	1.0	N	0.792	0.505	0.754199488981	gnomAD-4.0.0	2.47909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54315E-06	0	1.60143E-05
Y/H	None	None	0.999	N	0.711	0.472	0.598713980857	gnomAD-4.0.0	1.71075E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.24897E-05	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
Y/A	0.9388	likely_pathogenic	0.9627	pathogenic	-2.856	Highly Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
Y/C	0.5628	ambiguous	0.5905	pathogenic	-1.869	Destabilizing	1.0	D	0.792	deleterious	N	0.497319486	None	None	N
Y/D	0.9581	likely_pathogenic	0.9752	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.817	deleterious	N	0.518564066	None	None	N
Y/E	0.9869	likely_pathogenic	0.9925	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
Y/F	0.1815	likely_benign	0.1754	benign	-1.15	Destabilizing	0.073	N	0.322	neutral	N	0.451385097	None	None	N
Y/G	0.9375	likely_pathogenic	0.9622	pathogenic	-3.27	Highly Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
Y/H	0.7279	likely_pathogenic	0.7475	pathogenic	-1.736	Destabilizing	0.999	D	0.711	prob.delet.	N	0.505931658	None	None	N
Y/I	0.7918	likely_pathogenic	0.8571	pathogenic	-1.527	Destabilizing	0.95	D	0.675	neutral	None	None	None	None	N
Y/K	0.9777	likely_pathogenic	0.985	pathogenic	-2.019	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
Y/L	0.8098	likely_pathogenic	0.8705	pathogenic	-1.527	Destabilizing	0.845	D	0.474	neutral	None	None	None	None	N
Y/M	0.8998	likely_pathogenic	0.9308	pathogenic	-1.311	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
Y/N	0.8006	likely_pathogenic	0.8626	pathogenic	-2.64	Highly Destabilizing	1.0	D	0.798	deleterious	N	0.514689725	None	None	N
Y/P	0.9946	likely_pathogenic	0.9971	pathogenic	-1.977	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/Q	0.9637	likely_pathogenic	0.977	pathogenic	-2.407	Highly Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Y/R	0.9314	likely_pathogenic	0.9526	pathogenic	-1.727	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/S	0.8133	likely_pathogenic	0.8773	pathogenic	-3.176	Highly Destabilizing	0.999	D	0.751	deleterious	N	0.499445853	None	None	N
Y/T	0.8941	likely_pathogenic	0.9402	pathogenic	-2.879	Highly Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
Y/V	0.6661	likely_pathogenic	0.76	pathogenic	-1.977	Destabilizing	0.996	D	0.611	neutral	None	None	None	None	N
Y/W	0.7938	likely_pathogenic	0.8147	pathogenic	-0.546	Destabilizing	1.0	D	0.698	prob.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.