TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18895	56908;56909;56910	chr2:178599027;178599026;178599025	chr2:179463754;179463753;179463752
N2AB	17254	51985;51986;51987	chr2:178599027;178599026;178599025	chr2:179463754;179463753;179463752
N2A	16327	49204;49205;49206	chr2:178599027;178599026;178599025	chr2:179463754;179463753;179463752
N2B	9830	29713;29714;29715	chr2:178599027;178599026;178599025	chr2:179463754;179463753;179463752
Novex-1	9955	30088;30089;30090	chr2:178599027;178599026;178599025	chr2:179463754;179463753;179463752
Novex-2	10022	30289;30290;30291	chr2:178599027;178599026;178599025	chr2:179463754;179463753;179463752
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-25
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3959
• 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
S/C	rs1289916968	-0.077	0.999	N	0.437	0.293	0.385417323374	gnomAD-2.1.1	1.31E-05	None	None	None	None	N	None	6.71E-05	6.58E-05	None	0	0	None	0	None	0	0	0
S/C	rs1289916968	-0.077	0.999	N	0.437	0.293	0.385417323374	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	1.31079E-04	0	0	0	None	0	0	0	0	0
S/C	rs1289916968	-0.077	0.999	N	0.437	0.293	0.385417323374	gnomAD-4.0.0	6.29312E-06	None	None	None	None	N	None	8.1226E-05	7.10152E-05	None	0	0	None	0	0	0	0	0
S/G	rs1289916968	-0.565	0.826	N	0.344	0.098	0.257786959452	gnomAD-2.1.1	4.36E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.49E-06	0
S/G	rs1289916968	-0.565	0.826	N	0.344	0.098	0.257786959452	gnomAD-4.0.0	1.39178E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8194E-06	0	0
S/I	rs2052561080	None	0.996	N	0.492	0.347	0.496560916508	gnomAD-4.0.0	1.65177E-06	None	None	None	None	N	None	0	0	None	4.95688E-05	0	None	0	0	0	0	0
S/R	rs375403059	0.044	0.99	N	0.43	0.239	0.357519025918	gnomAD-2.1.1	4.33E-06	None	None	None	None	N	None	0	3.24E-05	None	0	0	None	0	None	0	0	0
S/R	rs375403059	0.044	0.99	N	0.43	0.239	0.357519025918	gnomAD-4.0.0	6.95199E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.09243E-07	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
S/A	0.0919	likely_benign	0.0871	benign	-0.267	Destabilizing	0.863	D	0.389	neutral	None	None	None	None	N
S/C	0.1711	likely_benign	0.1691	benign	-0.209	Destabilizing	0.999	D	0.437	neutral	N	0.503898925	None	None	N
S/D	0.5114	ambiguous	0.4433	ambiguous	0.136	Stabilizing	0.02	N	0.08	neutral	None	None	None	None	N
S/E	0.7012	likely_pathogenic	0.6068	pathogenic	0.026	Stabilizing	0.17	N	0.073	neutral	None	None	None	None	N
S/F	0.342	ambiguous	0.3308	benign	-0.976	Destabilizing	0.997	D	0.481	neutral	None	None	None	None	N
S/G	0.1256	likely_benign	0.1217	benign	-0.332	Destabilizing	0.826	D	0.344	neutral	N	0.480443276	None	None	N
S/H	0.5493	ambiguous	0.461	ambiguous	-0.833	Destabilizing	0.997	D	0.427	neutral	None	None	None	None	N
S/I	0.424	ambiguous	0.3726	ambiguous	-0.228	Destabilizing	0.996	D	0.492	neutral	N	0.506688514	None	None	N
S/K	0.9183	likely_pathogenic	0.8425	pathogenic	-0.337	Destabilizing	0.939	D	0.327	neutral	None	None	None	None	N
S/L	0.1515	likely_benign	0.1394	benign	-0.228	Destabilizing	0.969	D	0.445	neutral	None	None	None	None	N
S/M	0.2474	likely_benign	0.2199	benign	0.025	Stabilizing	0.999	D	0.41	neutral	None	None	None	None	N
S/N	0.2096	likely_benign	0.1739	benign	-0.045	Destabilizing	0.92	D	0.383	neutral	N	0.428494303	None	None	N
S/P	0.9461	likely_pathogenic	0.927	pathogenic	-0.215	Destabilizing	0.997	D	0.427	neutral	None	None	None	None	N
S/Q	0.6881	likely_pathogenic	0.5945	pathogenic	-0.317	Destabilizing	0.939	D	0.365	neutral	None	None	None	None	N
S/R	0.8926	likely_pathogenic	0.8226	pathogenic	-0.136	Destabilizing	0.99	D	0.43	neutral	N	0.490833628	None	None	N
S/T	0.1378	likely_benign	0.1231	benign	-0.168	Destabilizing	0.959	D	0.377	neutral	N	0.483656939	None	None	N
S/V	0.3319	likely_benign	0.2923	benign	-0.215	Destabilizing	0.969	D	0.463	neutral	None	None	None	None	N
S/W	0.5797	likely_pathogenic	0.5677	pathogenic	-1.009	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
S/Y	0.3242	likely_benign	0.2858	benign	-0.708	Destabilizing	0.997	D	0.478	neutral	None	None	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.