TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23736	71431;71432;71433	chr2:178574926;178574925;178574924	chr2:179439653;179439652;179439651
N2AB	22095	66508;66509;66510	chr2:178574926;178574925;178574924	chr2:179439653;179439652;179439651
N2A	21168	63727;63728;63729	chr2:178574926;178574925;178574924	chr2:179439653;179439652;179439651
N2B	14671	44236;44237;44238	chr2:178574926;178574925;178574924	chr2:179439653;179439652;179439651
Novex-1	14796	44611;44612;44613	chr2:178574926;178574925;178574924	chr2:179439653;179439652;179439651
Novex-2	14863	44812;44813;44814	chr2:178574926;178574925;178574924	chr2:179439653;179439652;179439651
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: Fn3-60
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.203
• 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/Y	None	None	0.815	N	0.555	0.17	0.394685799254	gnomAD-4.0.0	4.10734E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.3982E-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	0.52	ambiguous	0.5443	ambiguous	-2.285	Highly Destabilizing	0.543	D	0.524	neutral	None	None	None	None	N
F/C	0.3028	likely_benign	0.3246	benign	-1.888	Destabilizing	0.994	D	0.625	neutral	N	0.489161546	None	None	N
F/D	0.9217	likely_pathogenic	0.9194	pathogenic	-1.84	Destabilizing	0.984	D	0.666	neutral	None	None	None	None	N
F/E	0.8907	likely_pathogenic	0.9039	pathogenic	-1.621	Destabilizing	0.984	D	0.67	neutral	None	None	None	None	N
F/G	0.8554	likely_pathogenic	0.8671	pathogenic	-2.741	Highly Destabilizing	0.953	D	0.674	neutral	None	None	None	None	N
F/H	0.7925	likely_pathogenic	0.803	pathogenic	-1.389	Destabilizing	0.996	D	0.614	neutral	None	None	None	None	N
F/I	0.1231	likely_benign	0.1334	benign	-0.831	Destabilizing	0.007	N	0.262	neutral	N	0.404137363	None	None	N
F/K	0.8971	likely_pathogenic	0.91	pathogenic	-1.885	Destabilizing	0.953	D	0.679	prob.neutral	None	None	None	None	N
F/L	0.6844	likely_pathogenic	0.7455	pathogenic	-0.831	Destabilizing	0.001	N	0.189	neutral	N	0.439327372	None	None	N
F/M	0.3091	likely_benign	0.3523	ambiguous	-0.817	Destabilizing	0.91	D	0.593	neutral	None	None	None	None	N
F/N	0.7922	likely_pathogenic	0.7899	pathogenic	-2.305	Highly Destabilizing	0.984	D	0.667	neutral	None	None	None	None	N
F/P	0.8878	likely_pathogenic	0.8805	pathogenic	-1.322	Destabilizing	0.984	D	0.674	neutral	None	None	None	None	N
F/Q	0.8443	likely_pathogenic	0.8651	pathogenic	-2.117	Highly Destabilizing	0.984	D	0.671	neutral	None	None	None	None	N
F/R	0.8505	likely_pathogenic	0.8667	pathogenic	-1.618	Destabilizing	0.984	D	0.665	neutral	None	None	None	None	N
F/S	0.6233	likely_pathogenic	0.6254	pathogenic	-3.1	Highly Destabilizing	0.815	D	0.623	neutral	N	0.47020715	None	None	N
F/T	0.462	ambiguous	0.4855	ambiguous	-2.756	Highly Destabilizing	0.742	D	0.602	neutral	None	None	None	None	N
F/V	0.1563	likely_benign	0.1719	benign	-1.322	Destabilizing	0.134	N	0.437	neutral	N	0.419602674	None	None	N
F/W	0.5181	ambiguous	0.5193	ambiguous	-0.024	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
F/Y	0.2544	likely_benign	0.2664	benign	-0.389	Destabilizing	0.815	D	0.555	neutral	N	0.485294522	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.