TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27972	84139;84140;84141	chr2:178562218;178562217;178562216	chr2:179426945;179426944;179426943
N2AB	26331	79216;79217;79218	chr2:178562218;178562217;178562216	chr2:179426945;179426944;179426943
N2A	25404	76435;76436;76437	chr2:178562218;178562217;178562216	chr2:179426945;179426944;179426943
N2B	18907	56944;56945;56946	chr2:178562218;178562217;178562216	chr2:179426945;179426944;179426943
Novex-1	19032	57319;57320;57321	chr2:178562218;178562217;178562216	chr2:179426945;179426944;179426943
Novex-2	19099	57520;57521;57522	chr2:178562218;178562217;178562216	chr2:179426945;179426944;179426943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-142
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2202
• 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
F/S	rs1703936527	None	0.815	N	0.381	0.313	0.61599129918	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
F/A	0.8385	likely_pathogenic	0.8747	pathogenic	-2.312	Highly Destabilizing	0.59	D	0.381	neutral	None	None	None	None	N
F/C	0.4468	ambiguous	0.4911	ambiguous	-1.585	Destabilizing	0.994	D	0.397	neutral	N	0.483326153	None	None	N
F/D	0.9784	likely_pathogenic	0.9866	pathogenic	-1.335	Destabilizing	0.984	D	0.446	neutral	None	None	None	None	N
F/E	0.965	likely_pathogenic	0.9761	pathogenic	-1.18	Destabilizing	0.953	D	0.426	neutral	None	None	None	None	N
F/G	0.9528	likely_pathogenic	0.9668	pathogenic	-2.706	Highly Destabilizing	0.854	D	0.408	neutral	None	None	None	None	N
F/H	0.7874	likely_pathogenic	0.8225	pathogenic	-0.972	Destabilizing	0.91	D	0.336	neutral	None	None	None	None	N
F/I	0.2901	likely_benign	0.3073	benign	-1.09	Destabilizing	0.521	D	0.33	neutral	N	0.451304952	None	None	N
F/K	0.9496	likely_pathogenic	0.9633	pathogenic	-1.686	Destabilizing	0.953	D	0.424	neutral	None	None	None	None	N
F/L	0.928	likely_pathogenic	0.9298	pathogenic	-1.09	Destabilizing	0.309	N	0.307	neutral	N	0.470352073	None	None	N
F/M	0.6643	likely_pathogenic	0.6925	pathogenic	-0.914	Destabilizing	0.953	D	0.327	neutral	None	None	None	None	N
F/N	0.9283	likely_pathogenic	0.9486	pathogenic	-1.943	Destabilizing	0.953	D	0.46	neutral	None	None	None	None	N
F/P	0.9976	likely_pathogenic	0.9983	pathogenic	-1.497	Destabilizing	0.984	D	0.453	neutral	None	None	None	None	N
F/Q	0.9163	likely_pathogenic	0.9374	pathogenic	-1.881	Destabilizing	0.953	D	0.454	neutral	None	None	None	None	N
F/R	0.8913	likely_pathogenic	0.9183	pathogenic	-1.171	Destabilizing	0.953	D	0.456	neutral	None	None	None	None	N
F/S	0.8152	likely_pathogenic	0.8656	pathogenic	-2.758	Highly Destabilizing	0.815	D	0.381	neutral	N	0.482312195	None	None	N
F/T	0.8236	likely_pathogenic	0.8612	pathogenic	-2.493	Highly Destabilizing	0.742	D	0.366	neutral	None	None	None	None	N
F/V	0.2711	likely_benign	0.2936	benign	-1.497	Destabilizing	0.007	N	0.187	neutral	N	0.435543279	None	None	N
F/W	0.5429	ambiguous	0.6019	pathogenic	-0.178	Destabilizing	0.953	D	0.346	neutral	None	None	None	None	N
F/Y	0.1541	likely_benign	0.1669	benign	-0.511	Destabilizing	0.001	N	0.124	neutral	N	0.403631222	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.