TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28324	85195;85196;85197	chr2:178561162;178561161;178561160	chr2:179425889;179425888;179425887
N2AB	26683	80272;80273;80274	chr2:178561162;178561161;178561160	chr2:179425889;179425888;179425887
N2A	25756	77491;77492;77493	chr2:178561162;178561161;178561160	chr2:179425889;179425888;179425887
N2B	19259	58000;58001;58002	chr2:178561162;178561161;178561160	chr2:179425889;179425888;179425887
Novex-1	19384	58375;58376;58377	chr2:178561162;178561161;178561160	chr2:179425889;179425888;179425887
Novex-2	19451	58576;58577;58578	chr2:178561162;178561161;178561160	chr2:179425889;179425888;179425887
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: Fn3-94
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1569
• 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	0.014	N	0.515	0.286	0.208816687407	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85807E-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	0.6345	likely_pathogenic	0.6144	pathogenic	-1.051	Destabilizing	0.698	D	0.655	neutral	N	0.488716252	None	None	N
E/C	0.9571	likely_pathogenic	0.9604	pathogenic	-0.216	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
E/D	0.5773	likely_pathogenic	0.5831	pathogenic	-1.41	Destabilizing	0.006	N	0.315	neutral	N	0.474170396	None	None	N
E/F	0.9842	likely_pathogenic	0.9829	pathogenic	-0.651	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
E/G	0.8729	likely_pathogenic	0.8607	pathogenic	-1.486	Destabilizing	0.822	D	0.675	prob.neutral	D	0.526761641	None	None	N
E/H	0.9344	likely_pathogenic	0.936	pathogenic	-0.565	Destabilizing	0.994	D	0.648	neutral	None	None	None	None	N
E/I	0.8767	likely_pathogenic	0.8653	pathogenic	0.193	Stabilizing	0.978	D	0.798	deleterious	None	None	None	None	N
E/K	0.8692	likely_pathogenic	0.8571	pathogenic	-0.803	Destabilizing	0.014	N	0.515	neutral	N	0.511478259	None	None	N
E/L	0.9348	likely_pathogenic	0.9326	pathogenic	0.193	Stabilizing	0.956	D	0.731	prob.delet.	None	None	None	None	N
E/M	0.9026	likely_pathogenic	0.8965	pathogenic	0.896	Stabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
E/N	0.8831	likely_pathogenic	0.8855	pathogenic	-1.184	Destabilizing	0.754	D	0.619	neutral	None	None	None	None	N
E/P	0.9983	likely_pathogenic	0.9987	pathogenic	-0.206	Destabilizing	0.978	D	0.699	prob.neutral	None	None	None	None	N
E/Q	0.4483	ambiguous	0.4486	ambiguous	-0.851	Destabilizing	0.822	D	0.633	neutral	N	0.496567521	None	None	N
E/R	0.8949	likely_pathogenic	0.8896	pathogenic	-0.762	Destabilizing	0.915	D	0.635	neutral	None	None	None	None	N
E/S	0.7068	likely_pathogenic	0.706	pathogenic	-1.822	Destabilizing	0.86	D	0.629	neutral	None	None	None	None	N
E/T	0.8302	likely_pathogenic	0.8218	pathogenic	-1.399	Destabilizing	0.956	D	0.685	prob.neutral	None	None	None	None	N
E/V	0.7485	likely_pathogenic	0.7359	pathogenic	-0.206	Destabilizing	0.942	D	0.693	prob.neutral	N	0.475523068	None	None	N
E/W	0.9953	likely_pathogenic	0.9954	pathogenic	-0.703	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
E/Y	0.9699	likely_pathogenic	0.9698	pathogenic	-0.402	Destabilizing	0.993	D	0.753	deleterious	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.