TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8581	25966;25967;25968	chr2:178715673;178715672;178715671	chr2:179580400;179580399;179580398
N2AB	8264	25015;25016;25017	chr2:178715673;178715672;178715671	chr2:179580400;179580399;179580398
N2A	7337	22234;22235;22236	chr2:178715673;178715672;178715671	chr2:179580400;179580399;179580398
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-71
• Domain position: 33
• Structural Position: 46
• Q(SASA): 0.1657
• 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/F	None	None	0.007	D	0.602	0.578	0.689457545739	gnomAD-4.0.0	6.84702E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99863E-07	0	0
V/I	rs1014791707	None	None	N	0.285	0.178	0.518092603711	gnomAD-4.0.0	3.42351E-06	None	None	None	None	N	None	0	0	None	0	2.52309E-05	None	0	0	2.69959E-06	1.16198E-05	0
V/L	rs1014791707	-0.552	0.006	D	0.519	0.505	0.48286525802	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
V/L	rs1014791707	-0.552	0.006	D	0.519	0.505	0.48286525802	gnomAD-4.0.0	1.36941E-06	None	None	None	None	N	None	0	0	None	0	5.04643E-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	0.4896	ambiguous	0.562	ambiguous	-1.881	Destabilizing	0.335	N	0.695	prob.neutral	D	0.595909078	None	None	N
V/C	0.9277	likely_pathogenic	0.929	pathogenic	-1.057	Destabilizing	0.982	D	0.757	deleterious	None	None	None	None	N
V/D	0.976	likely_pathogenic	0.9723	pathogenic	-2.423	Highly Destabilizing	0.898	D	0.855	deleterious	D	0.634296608	None	None	N
V/E	0.9564	likely_pathogenic	0.9482	pathogenic	-2.255	Highly Destabilizing	0.654	D	0.84	deleterious	None	None	None	None	N
V/F	0.543	ambiguous	0.5226	ambiguous	-1.218	Destabilizing	0.007	N	0.602	neutral	D	0.537433946	None	None	N
V/G	0.6766	likely_pathogenic	0.7035	pathogenic	-2.334	Highly Destabilizing	0.923	D	0.809	deleterious	D	0.634296608	None	None	N
V/H	0.9837	likely_pathogenic	0.98	pathogenic	-2.012	Highly Destabilizing	0.986	D	0.837	deleterious	None	None	None	None	N
V/I	0.0978	likely_benign	0.09	benign	-0.637	Destabilizing	None	N	0.285	neutral	N	0.473422169	None	None	N
V/K	0.9705	likely_pathogenic	0.9634	pathogenic	-1.598	Destabilizing	0.805	D	0.839	deleterious	None	None	None	None	N
V/L	0.5144	ambiguous	0.4599	ambiguous	-0.637	Destabilizing	0.006	N	0.519	neutral	D	0.547165219	None	None	N
V/M	0.4386	ambiguous	0.4032	ambiguous	-0.432	Destabilizing	0.155	N	0.62	neutral	None	None	None	None	N
V/N	0.9332	likely_pathogenic	0.9255	pathogenic	-1.723	Destabilizing	0.651	D	0.85	deleterious	None	None	None	None	N
V/P	0.9016	likely_pathogenic	0.8941	pathogenic	-1.025	Destabilizing	0.651	D	0.849	deleterious	None	None	None	None	N
V/Q	0.9569	likely_pathogenic	0.9483	pathogenic	-1.682	Destabilizing	0.746	D	0.836	deleterious	None	None	None	None	N
V/R	0.9571	likely_pathogenic	0.9488	pathogenic	-1.31	Destabilizing	0.898	D	0.848	deleterious	None	None	None	None	N
V/S	0.7822	likely_pathogenic	0.8047	pathogenic	-2.242	Highly Destabilizing	0.826	D	0.809	deleterious	None	None	None	None	N
V/T	0.6003	likely_pathogenic	0.6205	pathogenic	-1.953	Destabilizing	0.212	N	0.711	prob.delet.	None	None	None	None	N
V/W	0.9818	likely_pathogenic	0.9794	pathogenic	-1.69	Destabilizing	0.996	D	0.836	deleterious	None	None	None	None	N
V/Y	0.9201	likely_pathogenic	0.9088	pathogenic	-1.292	Destabilizing	0.685	D	0.795	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.