TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5592	16999;17000;17001	chr2:178732195;178732194;178732193	chr2:179596922;179596921;179596920
N2AB	5275	16048;16049;16050	chr2:178732195;178732194;178732193	chr2:179596922;179596921;179596920
N2A	4348	13267;13268;13269	chr2:178732195;178732194;178732193	chr2:179596922;179596921;179596920
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-39
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.2079
• 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
M/I	rs879188937	-0.86	None	N	0.083	0.087	0.391930172978	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
M/I	rs879188937	-0.86	None	N	0.083	0.087	0.391930172978	gnomAD-4.0.0	8.89456E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.1693E-05	0	0
M/V	None	None	0.004	N	0.213	0.144	0.450733807028	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
M/A	0.5549	ambiguous	0.5735	pathogenic	-2.218	Highly Destabilizing	0.067	N	0.347	neutral	None	None	None	None	N
M/C	0.8154	likely_pathogenic	0.8153	pathogenic	-1.604	Destabilizing	0.935	D	0.443	neutral	None	None	None	None	N
M/D	0.9011	likely_pathogenic	0.9074	pathogenic	-0.985	Destabilizing	0.555	D	0.555	neutral	None	None	None	None	N
M/E	0.643	likely_pathogenic	0.6563	pathogenic	-0.866	Destabilizing	0.555	D	0.496	neutral	None	None	None	None	N
M/F	0.2859	likely_benign	0.282	benign	-0.887	Destabilizing	0.149	N	0.404	neutral	None	None	None	None	N
M/G	0.7301	likely_pathogenic	0.7532	pathogenic	-2.63	Highly Destabilizing	0.262	N	0.54	neutral	None	None	None	None	N
M/H	0.6311	likely_pathogenic	0.642	pathogenic	-1.799	Destabilizing	0.935	D	0.501	neutral	None	None	None	None	N
M/I	0.3197	likely_benign	0.3265	benign	-1.089	Destabilizing	None	N	0.083	neutral	N	0.464868895	None	None	N
M/K	0.2786	likely_benign	0.2822	benign	-0.982	Destabilizing	0.211	N	0.426	neutral	N	0.510357631	None	None	N
M/L	0.1429	likely_benign	0.1469	benign	-1.089	Destabilizing	None	N	0.077	neutral	N	0.477126117	None	None	N
M/N	0.6204	likely_pathogenic	0.6333	pathogenic	-1.006	Destabilizing	0.791	D	0.497	neutral	None	None	None	None	N
M/P	0.7736	likely_pathogenic	0.7829	pathogenic	-1.442	Destabilizing	0.791	D	0.499	neutral	None	None	None	None	N
M/Q	0.3319	likely_benign	0.3503	ambiguous	-0.919	Destabilizing	0.791	D	0.436	neutral	None	None	None	None	N
M/R	0.2762	likely_benign	0.287	benign	-0.71	Destabilizing	0.484	N	0.452	neutral	N	0.493658955	None	None	N
M/S	0.5458	ambiguous	0.5628	ambiguous	-1.69	Destabilizing	0.262	N	0.373	neutral	None	None	None	None	N
M/T	0.3653	ambiguous	0.3657	ambiguous	-1.444	Destabilizing	0.117	N	0.383	neutral	D	0.525093422	None	None	N
M/V	0.1465	likely_benign	0.1497	benign	-1.442	Destabilizing	0.004	N	0.213	neutral	N	0.503096423	None	None	N
M/W	0.6296	likely_pathogenic	0.6389	pathogenic	-0.925	Destabilizing	0.935	D	0.445	neutral	None	None	None	None	N
M/Y	0.5566	ambiguous	0.5592	ambiguous	-0.98	Destabilizing	0.555	D	0.459	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.