TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31816	95671;95672;95673	chr2:178545664;178545663;178545662	chr2:179410391;179410390;179410389
N2AB	30175	90748;90749;90750	chr2:178545664;178545663;178545662	chr2:179410391;179410390;179410389
N2A	29248	87967;87968;87969	chr2:178545664;178545663;178545662	chr2:179410391;179410390;179410389
N2B	22751	68476;68477;68478	chr2:178545664;178545663;178545662	chr2:179410391;179410390;179410389
Novex-1	22876	68851;68852;68853	chr2:178545664;178545663;178545662	chr2:179410391;179410390;179410389
Novex-2	22943	69052;69053;69054	chr2:178545664;178545663;178545662	chr2:179410391;179410390;179410389
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: Fn3-120
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.1779
• 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	0.001	N	0.241	0.068	0.192905019026	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
E/V	rs1226499081	0.243	0.101	N	0.483	0.212	0.159798565429	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65893E-04
E/V	rs1226499081	0.243	0.101	N	0.483	0.212	0.159798565429	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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	0.065	likely_benign	0.0583	benign	-0.438	Destabilizing	None	N	0.345	neutral	N	0.324766928	None	None	N
E/C	0.6286	likely_pathogenic	0.5997	pathogenic	-0.287	Destabilizing	0.94	D	0.639	neutral	None	None	None	None	N
E/D	0.2214	likely_benign	0.2177	benign	-0.574	Destabilizing	0.183	N	0.404	neutral	N	0.422915125	None	None	N
E/F	0.6721	likely_pathogenic	0.6425	pathogenic	0.095	Stabilizing	0.836	D	0.675	prob.neutral	None	None	None	None	N
E/G	0.1569	likely_benign	0.144	benign	-0.731	Destabilizing	0.001	N	0.476	neutral	N	0.433265404	None	None	N
E/H	0.5223	ambiguous	0.4918	ambiguous	0.215	Stabilizing	0.836	D	0.477	neutral	None	None	None	None	N
E/I	0.1665	likely_benign	0.1635	benign	0.333	Stabilizing	0.01	N	0.564	neutral	None	None	None	None	N
E/K	0.1769	likely_benign	0.1652	benign	0.088	Stabilizing	0.001	N	0.241	neutral	N	0.433785479	None	None	N
E/L	0.3079	likely_benign	0.2961	benign	0.333	Stabilizing	0.129	N	0.499	neutral	None	None	None	None	N
E/M	0.2656	likely_benign	0.2487	benign	0.367	Stabilizing	0.836	D	0.618	neutral	None	None	None	None	N
E/N	0.2765	likely_benign	0.2674	benign	-0.499	Destabilizing	0.228	N	0.429	neutral	None	None	None	None	N
E/P	0.2916	likely_benign	0.2567	benign	0.098	Stabilizing	0.593	D	0.547	neutral	None	None	None	None	N
E/Q	0.157	likely_benign	0.1473	benign	-0.377	Destabilizing	0.213	N	0.495	neutral	N	0.470879643	None	None	N
E/R	0.3243	likely_benign	0.3093	benign	0.418	Stabilizing	0.264	N	0.435	neutral	None	None	None	None	N
E/S	0.1771	likely_benign	0.1705	benign	-0.674	Destabilizing	0.004	N	0.208	neutral	None	None	None	None	N
E/T	0.1547	likely_benign	0.1431	benign	-0.422	Destabilizing	0.004	N	0.349	neutral	None	None	None	None	N
E/V	0.1023	likely_benign	0.0991	benign	0.098	Stabilizing	0.101	N	0.483	neutral	N	0.26035009	None	None	N
E/W	0.9069	likely_pathogenic	0.8817	pathogenic	0.348	Stabilizing	0.983	D	0.656	neutral	None	None	None	None	N
E/Y	0.5566	ambiguous	0.5195	ambiguous	0.363	Stabilizing	0.94	D	0.657	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.