TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3972	12139;12140;12141	chr2:178741319;178741318;178741317	chr2:179606046;179606045;179606044
N2AB	3655	11188;11189;11190	chr2:178741319;178741318;178741317	chr2:179606046;179606045;179606044
N2A	None	None	chr2:None	chr2:None
N2B	3609	11050;11051;11052	chr2:178741319;178741318;178741317	chr2:179606046;179606045;179606044
Novex-1	3734	11425;11426;11427	chr2:178741319;178741318;178741317	chr2:179606046;179606045;179606044
Novex-2	3801	11626;11627;11628	chr2:178741319;178741318;178741317	chr2:179606046;179606045;179606044
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-28
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1489
• 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	None	None	0.051	N	0.445	0.161	None	gnomAD-4.0.0	1.59108E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85786E-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	0.7781	likely_pathogenic	0.7328	pathogenic	-2.664	Highly Destabilizing	0.525	D	0.515	neutral	None	None	None	None	N
F/C	0.4229	ambiguous	0.3771	ambiguous	-1.377	Destabilizing	0.997	D	0.596	neutral	D	0.591538919	None	None	N
F/D	0.9084	likely_pathogenic	0.8807	pathogenic	-2.074	Highly Destabilizing	0.949	D	0.633	neutral	None	None	None	None	N
F/E	0.8387	likely_pathogenic	0.8049	pathogenic	-1.948	Destabilizing	0.842	D	0.63	neutral	None	None	None	None	N
F/G	0.8767	likely_pathogenic	0.8399	pathogenic	-3.036	Highly Destabilizing	0.728	D	0.569	neutral	None	None	None	None	N
F/H	0.5642	likely_pathogenic	0.5324	ambiguous	-1.293	Destabilizing	0.949	D	0.552	neutral	None	None	None	None	N
F/I	0.3372	likely_benign	0.3078	benign	-1.498	Destabilizing	0.669	D	0.477	neutral	N	0.472593464	None	None	N
F/K	0.8174	likely_pathogenic	0.796	pathogenic	-1.569	Destabilizing	0.842	D	0.627	neutral	None	None	None	None	N
F/L	0.836	likely_pathogenic	0.8168	pathogenic	-1.498	Destabilizing	0.005	N	0.196	neutral	N	0.44746544	None	None	N
F/M	0.6068	likely_pathogenic	0.5607	ambiguous	-1.121	Destabilizing	0.949	D	0.523	neutral	None	None	None	None	N
F/N	0.7308	likely_pathogenic	0.6955	pathogenic	-1.706	Destabilizing	0.949	D	0.638	neutral	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.998	pathogenic	-1.889	Destabilizing	0.974	D	0.625	neutral	None	None	None	None	N
F/Q	0.7414	likely_pathogenic	0.7067	pathogenic	-1.806	Destabilizing	0.974	D	0.631	neutral	None	None	None	None	N
F/R	0.7018	likely_pathogenic	0.6709	pathogenic	-0.864	Destabilizing	0.949	D	0.633	neutral	None	None	None	None	N
F/S	0.5921	likely_pathogenic	0.526	ambiguous	-2.459	Highly Destabilizing	0.051	N	0.445	neutral	N	0.446639268	None	None	N
F/T	0.7099	likely_pathogenic	0.6516	pathogenic	-2.242	Highly Destabilizing	0.728	D	0.546	neutral	None	None	None	None	N
F/V	0.3718	ambiguous	0.3353	benign	-1.889	Destabilizing	0.669	D	0.491	neutral	N	0.457970067	None	None	N
F/W	0.4468	ambiguous	0.4218	ambiguous	-0.431	Destabilizing	0.993	D	0.529	neutral	None	None	None	None	N
F/Y	0.1291	likely_benign	0.1374	benign	-0.725	Destabilizing	0.012	N	0.219	neutral	N	0.438028127	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.