TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31054	93385;93386;93387	chr2:178548466;178548465;178548464	chr2:179413193;179413192;179413191
N2AB	29413	88462;88463;88464	chr2:178548466;178548465;178548464	chr2:179413193;179413192;179413191
N2A	28486	85681;85682;85683	chr2:178548466;178548465;178548464	chr2:179413193;179413192;179413191
N2B	21989	66190;66191;66192	chr2:178548466;178548465;178548464	chr2:179413193;179413192;179413191
Novex-1	22114	66565;66566;66567	chr2:178548466;178548465;178548464	chr2:179413193;179413192;179413191
Novex-2	22181	66766;66767;66768	chr2:178548466;178548465;178548464	chr2:179413193;179413192;179413191
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-114
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1481
• 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	rs1049541565	None	0.896	N	0.629	0.37	0.32053947749	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.5723	likely_pathogenic	0.54	ambiguous	-1.363	Destabilizing	0.811	D	0.627	neutral	D	0.536837272	None	None	N
E/C	0.9625	likely_pathogenic	0.9574	pathogenic	-0.477	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
E/D	0.6452	likely_pathogenic	0.5698	pathogenic	-1.507	Destabilizing	0.011	N	0.359	neutral	D	0.523311405	None	None	N
E/F	0.972	likely_pathogenic	0.965	pathogenic	-1.049	Destabilizing	0.996	D	0.808	deleterious	None	None	None	None	N
E/G	0.6807	likely_pathogenic	0.5999	pathogenic	-1.74	Destabilizing	0.811	D	0.676	prob.neutral	D	0.538611699	None	None	N
E/H	0.8934	likely_pathogenic	0.8737	pathogenic	-0.859	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
E/I	0.9166	likely_pathogenic	0.9117	pathogenic	-0.278	Destabilizing	0.988	D	0.807	deleterious	None	None	None	None	N
E/K	0.7582	likely_pathogenic	0.7223	pathogenic	-1.202	Destabilizing	0.896	D	0.629	neutral	N	0.521580173	None	None	N
E/L	0.8898	likely_pathogenic	0.8642	pathogenic	-0.278	Destabilizing	0.976	D	0.762	deleterious	None	None	None	None	N
E/M	0.8419	likely_pathogenic	0.8287	pathogenic	0.397	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/N	0.8687	likely_pathogenic	0.828	pathogenic	-1.398	Destabilizing	0.919	D	0.643	neutral	None	None	None	None	N
E/P	0.9992	likely_pathogenic	0.9987	pathogenic	-0.626	Destabilizing	0.988	D	0.705	prob.neutral	None	None	None	None	N
E/Q	0.2297	likely_benign	0.2129	benign	-1.136	Destabilizing	0.984	D	0.661	neutral	N	0.519769668	None	None	N
E/R	0.8384	likely_pathogenic	0.8059	pathogenic	-1.059	Destabilizing	0.976	D	0.668	neutral	None	None	None	None	N
E/S	0.6136	likely_pathogenic	0.5747	pathogenic	-2.016	Highly Destabilizing	0.132	N	0.469	neutral	None	None	None	None	N
E/T	0.7907	likely_pathogenic	0.7663	pathogenic	-1.656	Destabilizing	0.851	D	0.651	neutral	None	None	None	None	N
E/V	0.7818	likely_pathogenic	0.7736	pathogenic	-0.626	Destabilizing	0.968	D	0.727	prob.delet.	D	0.532824801	None	None	N
E/W	0.9867	likely_pathogenic	0.9842	pathogenic	-1.114	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/Y	0.9621	likely_pathogenic	0.9549	pathogenic	-0.829	Destabilizing	0.996	D	0.781	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.