TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26745	80458;80459;80460	chr2:178565899;178565898;178565897	chr2:179430626;179430625;179430624
N2AB	25104	75535;75536;75537	chr2:178565899;178565898;178565897	chr2:179430626;179430625;179430624
N2A	24177	72754;72755;72756	chr2:178565899;178565898;178565897	chr2:179430626;179430625;179430624
N2B	17680	53263;53264;53265	chr2:178565899;178565898;178565897	chr2:179430626;179430625;179430624
Novex-1	17805	53638;53639;53640	chr2:178565899;178565898;178565897	chr2:179430626;179430625;179430624
Novex-2	17872	53839;53840;53841	chr2:178565899;178565898;178565897	chr2:179430626;179430625;179430624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-82
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.4906
• 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
E/Q	None	None	0.684	N	0.423	0.101	0.225215365344	gnomAD-4.0.0	6.36649E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14365E-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
E/A	0.1513	likely_benign	0.1405	benign	-0.763	Destabilizing	0.309	N	0.414	neutral	N	0.488582756	None	None	N
E/C	0.7493	likely_pathogenic	0.7549	pathogenic	-0.279	Destabilizing	0.996	D	0.554	neutral	None	None	None	None	N
E/D	0.0728	likely_benign	0.0833	benign	-0.679	Destabilizing	0.472	N	0.404	neutral	N	0.424840709	None	None	N
E/F	0.7591	likely_pathogenic	0.7375	pathogenic	-0.403	Destabilizing	0.953	D	0.573	neutral	None	None	None	None	N
E/G	0.1298	likely_benign	0.1226	benign	-1.03	Destabilizing	0.003	N	0.291	neutral	N	0.453643463	None	None	N
E/H	0.4854	ambiguous	0.4731	ambiguous	-0.341	Destabilizing	0.02	N	0.201	neutral	None	None	None	None	N
E/I	0.3822	ambiguous	0.3586	ambiguous	-0.065	Destabilizing	0.91	D	0.582	neutral	None	None	None	None	N
E/K	0.2219	likely_benign	0.184	benign	-0.078	Destabilizing	0.007	N	0.177	neutral	N	0.441212884	None	None	N
E/L	0.397	ambiguous	0.3671	ambiguous	-0.065	Destabilizing	0.742	D	0.522	neutral	None	None	None	None	N
E/M	0.4732	ambiguous	0.4371	ambiguous	0.213	Stabilizing	0.996	D	0.551	neutral	None	None	None	None	N
E/N	0.1804	likely_benign	0.1892	benign	-0.541	Destabilizing	0.742	D	0.377	neutral	None	None	None	None	N
E/P	0.3658	ambiguous	0.3342	benign	-0.277	Destabilizing	0.953	D	0.565	neutral	None	None	None	None	N
E/Q	0.1649	likely_benign	0.1506	benign	-0.474	Destabilizing	0.684	D	0.423	neutral	N	0.476306892	None	None	N
E/R	0.3487	ambiguous	0.3088	benign	0.208	Stabilizing	0.59	D	0.375	neutral	None	None	None	None	N
E/S	0.1547	likely_benign	0.1552	benign	-0.736	Destabilizing	0.373	N	0.397	neutral	None	None	None	None	N
E/T	0.1631	likely_benign	0.1671	benign	-0.514	Destabilizing	0.016	N	0.217	neutral	None	None	None	None	N
E/V	0.2323	likely_benign	0.214	benign	-0.277	Destabilizing	0.684	D	0.521	neutral	N	0.488582756	None	None	N
E/W	0.8861	likely_pathogenic	0.8728	pathogenic	-0.14	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
E/Y	0.6093	likely_pathogenic	0.5963	pathogenic	-0.142	Destabilizing	0.91	D	0.589	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.