TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33778	101557;101558;101559	chr2:178535283;178535282;178535281	chr2:179400010;179400009;179400008
N2AB	32137	96634;96635;96636	chr2:178535283;178535282;178535281	chr2:179400010;179400009;179400008
N2A	31210	93853;93854;93855	chr2:178535283;178535282;178535281	chr2:179400010;179400009;179400008
N2B	24713	74362;74363;74364	chr2:178535283;178535282;178535281	chr2:179400010;179400009;179400008
Novex-1	24838	74737;74738;74739	chr2:178535283;178535282;178535281	chr2:179400010;179400009;179400008
Novex-2	24905	74938;74939;74940	chr2:178535283;178535282;178535281	chr2:179400010;179400009;179400008
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: Fn3-132
• Domain position: 90
• Structural Position: 125
• Q(SASA): 0.6449
• 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/K	None	None	0.345	N	0.558	0.209	0.325263233342	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.1263	likely_benign	0.1319	benign	-0.201	Destabilizing	0.056	N	0.499	neutral	N	0.506016511	None	None	N
E/C	0.8276	likely_pathogenic	0.8477	pathogenic	-0.096	Destabilizing	0.969	D	0.724	deleterious	None	None	None	None	N
E/D	0.0931	likely_benign	0.1049	benign	-0.301	Destabilizing	None	N	0.174	neutral	N	0.48687339	None	None	N
E/F	0.7162	likely_pathogenic	0.7437	pathogenic	-0.189	Destabilizing	0.938	D	0.669	prob.neutral	None	None	None	None	N
E/G	0.1436	likely_benign	0.1289	benign	-0.34	Destabilizing	0.001	N	0.512	neutral	N	0.507344662	None	None	N
E/H	0.5296	ambiguous	0.5686	pathogenic	0.291	Stabilizing	0.915	D	0.555	neutral	None	None	None	None	N
E/I	0.3038	likely_benign	0.3472	ambiguous	0.115	Stabilizing	0.699	D	0.685	prob.delet.	None	None	None	None	N
E/K	0.1634	likely_benign	0.178	benign	0.421	Stabilizing	0.345	N	0.558	neutral	N	0.509864892	None	None	N
E/L	0.3183	likely_benign	0.3335	benign	0.115	Stabilizing	0.699	D	0.57	neutral	None	None	None	None	N
E/M	0.4306	ambiguous	0.4636	ambiguous	0.051	Stabilizing	0.827	D	0.707	prob.delet.	None	None	None	None	N
E/N	0.2193	likely_benign	0.2609	benign	0.137	Stabilizing	0.071	N	0.534	neutral	None	None	None	None	N
E/P	0.3479	ambiguous	0.3447	ambiguous	0.028	Stabilizing	0.257	N	0.594	neutral	None	None	None	None	N
E/Q	0.1612	likely_benign	0.1731	benign	0.152	Stabilizing	0.433	N	0.618	neutral	N	0.509864892	None	None	N
E/R	0.3225	likely_benign	0.3401	ambiguous	0.634	Stabilizing	0.832	D	0.58	neutral	None	None	None	None	N
E/S	0.1654	likely_benign	0.18	benign	-0.001	Destabilizing	0.274	N	0.479	neutral	None	None	None	None	N
E/T	0.1967	likely_benign	0.2237	benign	0.119	Stabilizing	0.343	N	0.572	neutral	None	None	None	None	N
E/V	0.1858	likely_benign	0.2138	benign	0.028	Stabilizing	0.555	D	0.577	neutral	D	0.526775785	None	None	N
E/W	0.9209	likely_pathogenic	0.9336	pathogenic	-0.095	Destabilizing	0.993	D	0.744	deleterious	None	None	None	None	N
E/Y	0.6331	likely_pathogenic	0.6669	pathogenic	0.044	Stabilizing	0.976	D	0.699	prob.delet.	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.