TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29669	89230;89231;89232	chr2:178554106;178554105;178554104	chr2:179418833;179418832;179418831
N2AB	28028	84307;84308;84309	chr2:178554106;178554105;178554104	chr2:179418833;179418832;179418831
N2A	27101	81526;81527;81528	chr2:178554106;178554105;178554104	chr2:179418833;179418832;179418831
N2B	20604	62035;62036;62037	chr2:178554106;178554105;178554104	chr2:179418833;179418832;179418831
Novex-1	20729	62410;62411;62412	chr2:178554106;178554105;178554104	chr2:179418833;179418832;179418831
Novex-2	20796	62611;62612;62613	chr2:178554106;178554105;178554104	chr2:179418833;179418832;179418831
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: Fn3-104
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1369
• 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	0.055	N	0.605	0.216	0.317378411342	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85794E-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	0.5504	ambiguous	0.5722	pathogenic	-2.951	Highly Destabilizing	0.031	N	0.561	neutral	None	None	None	None	N
F/C	0.2126	likely_benign	0.2165	benign	-1.542	Destabilizing	0.56	D	0.637	neutral	N	0.44902429	None	None	N
F/D	0.7632	likely_pathogenic	0.7838	pathogenic	-2.38	Highly Destabilizing	0.136	N	0.661	neutral	None	None	None	None	N
F/E	0.7893	likely_pathogenic	0.798	pathogenic	-2.25	Highly Destabilizing	0.136	N	0.611	neutral	None	None	None	None	N
F/G	0.8116	likely_pathogenic	0.8388	pathogenic	-3.328	Highly Destabilizing	0.136	N	0.618	neutral	None	None	None	None	N
F/H	0.3189	likely_benign	0.3213	benign	-1.524	Destabilizing	0.214	N	0.643	neutral	None	None	None	None	N
F/I	0.105	likely_benign	0.1099	benign	-1.753	Destabilizing	None	N	0.289	neutral	N	0.329812962	None	None	N
F/K	0.7805	likely_pathogenic	0.7948	pathogenic	-1.774	Destabilizing	0.072	N	0.608	neutral	None	None	None	None	N
F/L	0.6029	likely_pathogenic	0.634	pathogenic	-1.753	Destabilizing	None	N	0.217	neutral	N	0.369792716	None	None	N
F/M	0.3554	ambiguous	0.3757	ambiguous	-1.308	Destabilizing	0.003	N	0.391	neutral	None	None	None	None	N
F/N	0.4502	ambiguous	0.4713	ambiguous	-1.902	Destabilizing	0.356	N	0.661	neutral	None	None	None	None	N
F/P	0.9944	likely_pathogenic	0.9963	pathogenic	-2.157	Highly Destabilizing	0.628	D	0.663	neutral	None	None	None	None	N
F/Q	0.6005	likely_pathogenic	0.6097	pathogenic	-2.019	Highly Destabilizing	0.356	N	0.662	neutral	None	None	None	None	N
F/R	0.6714	likely_pathogenic	0.6894	pathogenic	-1.019	Destabilizing	0.214	N	0.655	neutral	None	None	None	None	N
F/S	0.3594	ambiguous	0.3863	ambiguous	-2.663	Highly Destabilizing	0.055	N	0.605	neutral	N	0.427838155	None	None	N
F/T	0.3782	ambiguous	0.3866	ambiguous	-2.443	Highly Destabilizing	0.072	N	0.603	neutral	None	None	None	None	N
F/V	0.1346	likely_benign	0.1389	benign	-2.157	Highly Destabilizing	0.002	N	0.489	neutral	N	0.34266483	None	None	N
F/W	0.4141	ambiguous	0.4467	ambiguous	-0.62	Destabilizing	0.356	N	0.627	neutral	None	None	None	None	N
F/Y	0.083	likely_benign	0.085	benign	-0.969	Destabilizing	None	N	0.194	neutral	N	0.376046684	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.