TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19331	58216;58217;58218	chr2:178594503;178594502;178594501	chr2:179459230;179459229;179459228
N2AB	17690	53293;53294;53295	chr2:178594503;178594502;178594501	chr2:179459230;179459229;179459228
N2A	16763	50512;50513;50514	chr2:178594503;178594502;178594501	chr2:179459230;179459229;179459228
N2B	10266	31021;31022;31023	chr2:178594503;178594502;178594501	chr2:179459230;179459229;179459228
Novex-1	10391	31396;31397;31398	chr2:178594503;178594502;178594501	chr2:179459230;179459229;179459228
Novex-2	10458	31597;31598;31599	chr2:178594503;178594502;178594501	chr2:179459230;179459229;179459228
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: Fn3-28
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.3064
• 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/L	rs1449016899	-1.079	0.999	N	0.554	0.485	0.550210968228	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
F/L	rs1449016899	-1.079	0.999	N	0.554	0.485	0.550210968228	gnomAD-4.0.0	2.73747E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59854E-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	0.993	likely_pathogenic	0.9907	pathogenic	-2.46	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
F/C	0.9686	likely_pathogenic	0.9571	pathogenic	-1.071	Destabilizing	1.0	D	0.774	deleterious	N	0.475038861	None	None	N
F/D	0.9928	likely_pathogenic	0.9918	pathogenic	-1.337	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
F/E	0.9959	likely_pathogenic	0.9957	pathogenic	-1.293	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/G	0.9934	likely_pathogenic	0.992	pathogenic	-2.764	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/H	0.9412	likely_pathogenic	0.9341	pathogenic	-0.997	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
F/I	0.9541	likely_pathogenic	0.9364	pathogenic	-1.548	Destabilizing	1.0	D	0.739	prob.delet.	N	0.482925673	None	None	N
F/K	0.9969	likely_pathogenic	0.9967	pathogenic	-1.046	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
F/L	0.9961	likely_pathogenic	0.9951	pathogenic	-1.548	Destabilizing	0.999	D	0.554	neutral	N	0.518940162	None	None	N
F/M	0.9715	likely_pathogenic	0.9668	pathogenic	-1.1	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
F/N	0.9712	likely_pathogenic	0.9696	pathogenic	-0.943	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
F/P	0.9972	likely_pathogenic	0.9966	pathogenic	-1.846	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
F/Q	0.9918	likely_pathogenic	0.9918	pathogenic	-1.179	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
F/R	0.9942	likely_pathogenic	0.9934	pathogenic	-0.235	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
F/S	0.9822	likely_pathogenic	0.9763	pathogenic	-1.74	Destabilizing	1.0	D	0.803	deleterious	N	0.480897757	None	None	N
F/T	0.9903	likely_pathogenic	0.9873	pathogenic	-1.607	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
F/V	0.9658	likely_pathogenic	0.9527	pathogenic	-1.846	Destabilizing	1.0	D	0.778	deleterious	N	0.482418694	None	None	N
F/W	0.4385	ambiguous	0.3931	ambiguous	-0.829	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
F/Y	0.1794	likely_benign	0.1745	benign	-0.964	Destabilizing	0.999	D	0.525	neutral	N	0.470495641	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.