TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4934	15025;15026;15027	chr2:178735646;178735645;178735644	chr2:179600373;179600372;179600371
N2AB	4617	14074;14075;14076	chr2:178735646;178735645;178735644	chr2:179600373;179600372;179600371
N2A	3690	11293;11294;11295	chr2:178735646;178735645;178735644	chr2:179600373;179600372;179600371
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-32
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2191
• 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	None	None	None	N	0.321	0.396	0.434384183301	gnomAD-4.0.0	2.05274E-06	None	None	None	None	N	None	2.98739E-05	0	None	0	0	None	0	0	1.79892E-06	0	0
Y/D	rs2081313340	None	0.317	D	0.593	0.448	0.651643192601	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/D	rs2081313340	None	0.317	D	0.593	0.448	0.651643192601	gnomAD-4.0.0	6.57134E-06	None	None	None	None	N	None	2.41231E-05	0	None	0	0	None	0	0	0	0	0
Y/H	None	None	None	N	0.287	0.23	0.273938319068	gnomAD-4.0.0	1.59148E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85819E-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
Y/A	0.403	ambiguous	0.4594	ambiguous	-2.99	Highly Destabilizing	0.067	N	0.438	neutral	None	None	None	None	N
Y/C	0.082	likely_benign	0.0979	benign	-1.929	Destabilizing	None	N	0.321	neutral	N	0.514303215	None	None	N
Y/D	0.4212	ambiguous	0.49	ambiguous	-2.69	Highly Destabilizing	0.317	N	0.593	neutral	D	0.558899366	None	None	N
Y/E	0.6227	likely_pathogenic	0.6816	pathogenic	-2.536	Highly Destabilizing	0.081	N	0.557	neutral	None	None	None	None	N
Y/F	0.0998	likely_benign	0.1103	benign	-1.243	Destabilizing	0.117	N	0.495	neutral	N	0.463611292	None	None	N
Y/G	0.3716	ambiguous	0.4161	ambiguous	-3.382	Highly Destabilizing	0.149	N	0.574	neutral	None	None	None	None	N
Y/H	0.1402	likely_benign	0.1579	benign	-1.908	Destabilizing	None	N	0.287	neutral	N	0.506421267	None	None	N
Y/I	0.3124	likely_benign	0.3454	ambiguous	-1.723	Destabilizing	0.081	N	0.502	neutral	None	None	None	None	N
Y/K	0.5734	likely_pathogenic	0.6252	pathogenic	-2.36	Highly Destabilizing	0.149	N	0.557	neutral	None	None	None	None	N
Y/L	0.3493	ambiguous	0.3741	ambiguous	-1.723	Destabilizing	0.001	N	0.206	neutral	None	None	None	None	N
Y/M	0.4735	ambiguous	0.5256	ambiguous	-1.425	Destabilizing	0.38	N	0.528	neutral	None	None	None	None	N
Y/N	0.1776	likely_benign	0.2106	benign	-2.949	Highly Destabilizing	0.188	N	0.57	neutral	D	0.600927703	None	None	N
Y/P	0.8695	likely_pathogenic	0.8935	pathogenic	-2.153	Highly Destabilizing	0.555	D	0.599	neutral	None	None	None	None	N
Y/Q	0.3751	ambiguous	0.4285	ambiguous	-2.747	Highly Destabilizing	0.38	N	0.546	neutral	None	None	None	None	N
Y/R	0.3681	ambiguous	0.4056	ambiguous	-2.014	Highly Destabilizing	0.38	N	0.562	neutral	None	None	None	None	N
Y/S	0.1894	likely_benign	0.2186	benign	-3.353	Highly Destabilizing	0.117	N	0.521	neutral	D	0.540731517	None	None	N
Y/T	0.3119	likely_benign	0.3588	ambiguous	-3.087	Highly Destabilizing	0.149	N	0.538	neutral	None	None	None	None	N
Y/V	0.2575	likely_benign	0.285	benign	-2.153	Highly Destabilizing	0.081	N	0.517	neutral	None	None	None	None	N
Y/W	0.3792	ambiguous	0.4066	ambiguous	-0.718	Destabilizing	0.935	D	0.513	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.