TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22143	66652;66653;66654	chr2:178581942;178581941;178581940	chr2:179446669;179446668;179446667
N2AB	20502	61729;61730;61731	chr2:178581942;178581941;178581940	chr2:179446669;179446668;179446667
N2A	19575	58948;58949;58950	chr2:178581942;178581941;178581940	chr2:179446669;179446668;179446667
N2B	13078	39457;39458;39459	chr2:178581942;178581941;178581940	chr2:179446669;179446668;179446667
Novex-1	13203	39832;39833;39834	chr2:178581942;178581941;178581940	chr2:179446669;179446668;179446667
Novex-2	13270	40033;40034;40035	chr2:178581942;178581941;178581940	chr2:179446669;179446668;179446667
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-48
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.9297
• 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
D/N	None	None	0.799	N	0.682	0.225	0.350964488264	gnomAD-4.0.0	6.84453E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99687E-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
D/A	0.118	likely_benign	0.1248	benign	-0.372	Destabilizing	0.012	N	0.515	neutral	N	0.457331556	None	None	N
D/C	0.5757	likely_pathogenic	0.5742	pathogenic	0.032	Stabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
D/E	0.0966	likely_benign	0.099	benign	-0.378	Destabilizing	0.119	N	0.249	neutral	N	0.415714219	None	None	N
D/F	0.509	ambiguous	0.509	ambiguous	-0.275	Destabilizing	0.974	D	0.779	deleterious	None	None	None	None	N
D/G	0.1767	likely_benign	0.1847	benign	-0.591	Destabilizing	0.012	N	0.451	neutral	N	0.49417779	None	None	N
D/H	0.3178	likely_benign	0.3072	benign	-0.246	Destabilizing	0.997	D	0.668	prob.neutral	N	0.475479707	None	None	N
D/I	0.246	likely_benign	0.2541	benign	0.164	Stabilizing	0.949	D	0.8	deleterious	None	None	None	None	N
D/K	0.3249	likely_benign	0.3146	benign	0.24	Stabilizing	0.841	D	0.625	neutral	None	None	None	None	N
D/L	0.2424	likely_benign	0.2567	benign	0.164	Stabilizing	0.949	D	0.627	neutral	None	None	None	None	N
D/M	0.4449	ambiguous	0.4594	ambiguous	0.384	Stabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
D/N	0.1136	likely_benign	0.1106	benign	-0.076	Destabilizing	0.799	D	0.682	prob.neutral	N	0.505952222	None	None	N
D/P	0.3449	ambiguous	0.3673	ambiguous	0.008	Stabilizing	0.974	D	0.692	prob.delet.	None	None	None	None	N
D/Q	0.2822	likely_benign	0.2893	benign	-0.043	Destabilizing	0.949	D	0.668	prob.neutral	None	None	None	None	N
D/R	0.4077	ambiguous	0.39	ambiguous	0.375	Stabilizing	0.949	D	0.846	deleterious	None	None	None	None	N
D/S	0.1224	likely_benign	0.1255	benign	-0.196	Destabilizing	0.725	D	0.553	neutral	None	None	None	None	N
D/T	0.2028	likely_benign	0.2086	benign	-0.024	Destabilizing	0.949	D	0.615	neutral	None	None	None	None	N
D/V	0.1472	likely_benign	0.152	benign	0.008	Stabilizing	0.875	D	0.572	neutral	N	0.501373121	None	None	N
D/W	0.8639	likely_pathogenic	0.8631	pathogenic	-0.12	Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
D/Y	0.2416	likely_benign	0.2363	benign	-0.031	Destabilizing	0.989	D	0.777	deleterious	N	0.480341552	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.