TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8335	25228;25229;25230	chr2:178718003;178718002;178718001	chr2:179582730;179582729;179582728
N2AB	8018	24277;24278;24279	chr2:178718003;178718002;178718001	chr2:179582730;179582729;179582728
N2A	7091	21496;21497;21498	chr2:178718003;178718002;178718001	chr2:179582730;179582729;179582728
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-68
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.2275
• 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
S/A	rs773006091	-0.6	0.005	N	0.427	0.123	0.0401082797425	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
S/A	rs773006091	-0.6	0.005	N	0.427	0.123	0.0401082797425	gnomAD-4.0.0	6.84237E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99517E-07	0	0
S/T	None	None	None	N	0.203	0.093	0.0297737177859	gnomAD-4.0.0	6.84237E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99517E-07	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
S/A	0.0858	likely_benign	0.0973	benign	-1.078	Destabilizing	0.005	N	0.427	neutral	N	0.520167605	None	None	N
S/C	0.1021	likely_benign	0.1185	benign	-0.491	Destabilizing	0.356	N	0.605	neutral	None	None	None	None	N
S/D	0.4337	ambiguous	0.5663	pathogenic	-0.91	Destabilizing	0.031	N	0.475	neutral	None	None	None	None	N
S/E	0.4467	ambiguous	0.53	ambiguous	-0.688	Destabilizing	0.016	N	0.449	neutral	None	None	None	None	N
S/F	0.1391	likely_benign	0.1709	benign	-1.024	Destabilizing	0.038	N	0.627	neutral	None	None	None	None	N
S/G	0.1324	likely_benign	0.1763	benign	-1.464	Destabilizing	0.031	N	0.441	neutral	None	None	None	None	N
S/H	0.2086	likely_benign	0.2509	benign	-1.533	Destabilizing	0.214	N	0.587	neutral	None	None	None	None	N
S/I	0.0866	likely_benign	0.0949	benign	-0.071	Destabilizing	None	N	0.473	neutral	None	None	None	None	N
S/K	0.4822	ambiguous	0.5885	pathogenic	0.402	Stabilizing	0.016	N	0.451	neutral	None	None	None	None	N
S/L	0.0863	likely_benign	0.102	benign	-0.071	Destabilizing	0.005	N	0.553	neutral	N	0.500581766	None	None	N
S/M	0.1311	likely_benign	0.1374	benign	-0.196	Destabilizing	0.214	N	0.589	neutral	None	None	None	None	N
S/N	0.1291	likely_benign	0.1773	benign	-0.295	Destabilizing	0.072	N	0.495	neutral	None	None	None	None	N
S/P	0.8956	likely_pathogenic	0.9591	pathogenic	-0.377	Destabilizing	0.106	N	0.597	neutral	N	0.513902804	None	None	N
S/Q	0.357	ambiguous	0.4134	ambiguous	-0.069	Destabilizing	0.003	N	0.309	neutral	None	None	None	None	N
S/R	0.324	likely_benign	0.4205	ambiguous	-0.05	Destabilizing	0.072	N	0.602	neutral	None	None	None	None	N
S/T	0.0523	likely_benign	0.0481	benign	-0.102	Destabilizing	None	N	0.203	neutral	N	0.391891289	None	None	N
S/V	0.1098	likely_benign	0.1201	benign	-0.377	Destabilizing	None	N	0.465	neutral	None	None	None	None	N
S/W	0.2527	likely_benign	0.3086	benign	-1.103	Destabilizing	0.356	N	0.653	neutral	None	None	None	None	N
S/Y	0.1289	likely_benign	0.1589	benign	-0.688	Destabilizing	None	N	0.449	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.