TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17909	53950;53951;53952	chr2:178605570;178605569;178605568	chr2:179470297;179470296;179470295
N2AB	16268	49027;49028;49029	chr2:178605570;178605569;178605568	chr2:179470297;179470296;179470295
N2A	15341	46246;46247;46248	chr2:178605570;178605569;178605568	chr2:179470297;179470296;179470295
N2B	8844	26755;26756;26757	chr2:178605570;178605569;178605568	chr2:179470297;179470296;179470295
Novex-1	8969	27130;27131;27132	chr2:178605570;178605569;178605568	chr2:179470297;179470296;179470295
Novex-2	9036	27331;27332;27333	chr2:178605570;178605569;178605568	chr2:179470297;179470296;179470295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-18
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2532
• 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	rs1328997528	-1.459	0.949	N	0.595	0.273	0.609492077976	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
F/S	rs1328997528	-1.459	0.949	N	0.595	0.273	0.609492077976	gnomAD-4.0.0	1.59435E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86512E-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	0.9656	likely_pathogenic	0.9486	pathogenic	-2.485	Highly Destabilizing	0.775	D	0.574	neutral	None	None	None	None	N
F/C	0.9257	likely_pathogenic	0.8701	pathogenic	-1.128	Destabilizing	0.995	D	0.663	neutral	N	0.491013068	None	None	N
F/D	0.9779	likely_pathogenic	0.9669	pathogenic	-1.576	Destabilizing	0.987	D	0.673	neutral	None	None	None	None	N
F/E	0.99	likely_pathogenic	0.9879	pathogenic	-1.528	Destabilizing	0.961	D	0.666	neutral	None	None	None	None	N
F/G	0.9782	likely_pathogenic	0.9691	pathogenic	-2.783	Highly Destabilizing	0.923	D	0.584	neutral	None	None	None	None	N
F/H	0.8984	likely_pathogenic	0.8506	pathogenic	-1.02	Destabilizing	0.923	D	0.617	neutral	None	None	None	None	N
F/I	0.8911	likely_pathogenic	0.8339	pathogenic	-1.59	Destabilizing	0.901	D	0.536	neutral	N	0.466107957	None	None	N
F/K	0.9933	likely_pathogenic	0.9911	pathogenic	-1.151	Destabilizing	0.961	D	0.671	neutral	None	None	None	None	N
F/L	0.9841	likely_pathogenic	0.9781	pathogenic	-1.59	Destabilizing	0.565	D	0.546	neutral	N	0.512126046	None	None	N
F/M	0.9321	likely_pathogenic	0.908	pathogenic	-1.182	Destabilizing	0.987	D	0.569	neutral	None	None	None	None	N
F/N	0.9546	likely_pathogenic	0.9296	pathogenic	-1.097	Destabilizing	0.961	D	0.675	neutral	None	None	None	None	N
F/P	0.9892	likely_pathogenic	0.983	pathogenic	-1.882	Destabilizing	0.987	D	0.67	neutral	None	None	None	None	N
F/Q	0.9859	likely_pathogenic	0.9837	pathogenic	-1.336	Destabilizing	0.987	D	0.675	neutral	None	None	None	None	N
F/R	0.9857	likely_pathogenic	0.9825	pathogenic	-0.327	Destabilizing	0.961	D	0.673	neutral	None	None	None	None	N
F/S	0.933	likely_pathogenic	0.8986	pathogenic	-1.839	Destabilizing	0.949	D	0.595	neutral	N	0.477717752	None	None	N
F/T	0.9582	likely_pathogenic	0.9302	pathogenic	-1.707	Destabilizing	0.961	D	0.592	neutral	None	None	None	None	N
F/V	0.8823	likely_pathogenic	0.8274	pathogenic	-1.882	Destabilizing	0.722	D	0.534	neutral	N	0.461726637	None	None	N
F/W	0.386	ambiguous	0.3398	benign	-0.781	Destabilizing	0.024	N	0.305	neutral	None	None	None	None	N
F/Y	0.1962	likely_benign	0.1429	benign	-0.925	Destabilizing	0.003	N	0.223	neutral	N	0.463065449	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.