TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7171	21736;21737;21738	chr2:178723589;178723588;178723587	chr2:179588316;179588315;179588314
N2AB	6854	20785;20786;20787	chr2:178723589;178723588;178723587	chr2:179588316;179588315;179588314
N2A	5927	18004;18005;18006	chr2:178723589;178723588;178723587	chr2:179588316;179588315;179588314
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-56
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2324
• 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	None	None	0.999	N	0.589	0.366	0.380730819819	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79924E-06	0	0
F/V	rs750008949	-2.172	1.0	N	0.781	0.468	0.721980647632	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
F/V	rs750008949	-2.172	1.0	N	0.781	0.468	0.721980647632	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/V	rs750008949	-2.172	1.0	N	0.781	0.468	0.721980647632	gnomAD-4.0.0	2.04564E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.79759E-05	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	0.8692	likely_pathogenic	0.8861	pathogenic	-2.553	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
F/C	0.6526	likely_pathogenic	0.6873	pathogenic	-1.267	Destabilizing	1.0	D	0.803	deleterious	N	0.518744746	None	None	N
F/D	0.9491	likely_pathogenic	0.9583	pathogenic	-1.828	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
F/E	0.9261	likely_pathogenic	0.9354	pathogenic	-1.725	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
F/G	0.9119	likely_pathogenic	0.9265	pathogenic	-2.904	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
F/H	0.624	likely_pathogenic	0.6498	pathogenic	-1.171	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
F/I	0.5123	ambiguous	0.524	ambiguous	-1.464	Destabilizing	1.0	D	0.75	deleterious	N	0.477634711	None	None	N
F/K	0.8514	likely_pathogenic	0.8636	pathogenic	-1.327	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
F/L	0.9096	likely_pathogenic	0.9135	pathogenic	-1.464	Destabilizing	0.999	D	0.589	neutral	N	0.505058427	None	None	N
F/M	0.74	likely_pathogenic	0.7538	pathogenic	-1.097	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
F/N	0.8052	likely_pathogenic	0.8283	pathogenic	-1.4	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/P	0.999	likely_pathogenic	0.9992	pathogenic	-1.826	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
F/Q	0.7952	likely_pathogenic	0.82	pathogenic	-1.542	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
F/R	0.737	likely_pathogenic	0.7589	pathogenic	-0.614	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
F/S	0.6756	likely_pathogenic	0.7152	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.798	deleterious	N	0.455340174	None	None	N
F/T	0.8449	likely_pathogenic	0.8565	pathogenic	-1.977	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
F/V	0.5312	ambiguous	0.5488	ambiguous	-1.826	Destabilizing	1.0	D	0.781	deleterious	N	0.474836781	None	None	N
F/W	0.578	likely_pathogenic	0.5795	pathogenic	-0.505	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
F/Y	0.1772	likely_benign	0.1791	benign	-0.736	Destabilizing	0.999	D	0.511	neutral	N	0.488550179	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.