TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7516	22771;22772;22773	chr2:178722117;178722116;178722115	chr2:179586844;179586843;179586842
N2AB	7199	21820;21821;21822	chr2:178722117;178722116;178722115	chr2:179586844;179586843;179586842
N2A	6272	19039;19040;19041	chr2:178722117;178722116;178722115	chr2:179586844;179586843;179586842
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-60
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5797
• 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	rs2078474988	None	0.148	N	0.229	0.256	0.531922418639	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/S	rs2078474988	None	0.148	N	0.229	0.256	0.531922418639	gnomAD-4.0.0	6.57194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47029E-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	0.309	likely_benign	0.342	ambiguous	-1.291	Destabilizing	0.347	N	0.201	neutral	None	None	None	None	N
F/C	0.2831	likely_benign	0.3118	benign	-0.367	Destabilizing	0.99	D	0.256	neutral	N	0.492711645	None	None	N
F/D	0.6135	likely_pathogenic	0.6616	pathogenic	0.506	Stabilizing	0.855	D	0.329	neutral	None	None	None	None	N
F/E	0.6249	likely_pathogenic	0.6638	pathogenic	0.507	Stabilizing	0.639	D	0.311	neutral	None	None	None	None	N
F/G	0.6386	likely_pathogenic	0.6982	pathogenic	-1.529	Destabilizing	0.709	D	0.277	neutral	None	None	None	None	N
F/H	0.371	ambiguous	0.406	ambiguous	0.031	Stabilizing	0.975	D	0.252	neutral	None	None	None	None	N
F/I	0.1018	likely_benign	0.1205	benign	-0.651	Destabilizing	0.01	N	0.145	neutral	N	0.46587176	None	None	N
F/K	0.6174	likely_pathogenic	0.6504	pathogenic	-0.272	Destabilizing	0.55	D	0.287	neutral	None	None	None	None	N
F/L	0.6542	likely_pathogenic	0.6941	pathogenic	-0.651	Destabilizing	0.002	N	0.158	neutral	N	0.450883665	None	None	N
F/M	0.3866	ambiguous	0.4298	ambiguous	-0.435	Destabilizing	0.445	N	0.255	neutral	None	None	None	None	N
F/N	0.4204	ambiguous	0.4596	ambiguous	-0.186	Destabilizing	0.855	D	0.351	neutral	None	None	None	None	N
F/P	0.9858	likely_pathogenic	0.9874	pathogenic	-0.848	Destabilizing	0.992	D	0.355	neutral	None	None	None	None	N
F/Q	0.5145	ambiguous	0.5582	ambiguous	-0.272	Destabilizing	0.861	D	0.351	neutral	None	None	None	None	N
F/R	0.4311	ambiguous	0.4637	ambiguous	0.288	Stabilizing	0.008	N	0.199	neutral	None	None	None	None	N
F/S	0.1923	likely_benign	0.2168	benign	-0.933	Destabilizing	0.148	N	0.229	neutral	N	0.402897717	None	None	N
F/T	0.2443	likely_benign	0.2956	benign	-0.84	Destabilizing	0.032	N	0.194	neutral	None	None	None	None	N
F/V	0.0969	likely_benign	0.1111	benign	-0.848	Destabilizing	0.002	N	0.151	neutral	N	0.387658905	None	None	N
F/W	0.5247	ambiguous	0.5646	pathogenic	-0.289	Destabilizing	0.996	D	0.296	neutral	None	None	None	None	N
F/Y	0.1379	likely_benign	0.145	benign	-0.337	Destabilizing	0.625	D	0.245	neutral	N	0.458252354	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.