TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21306	64141;64142;64143	chr2:178587295;178587294;178587293	chr2:179452022;179452021;179452020
N2AB	19665	59218;59219;59220	chr2:178587295;178587294;178587293	chr2:179452022;179452021;179452020
N2A	18738	56437;56438;56439	chr2:178587295;178587294;178587293	chr2:179452022;179452021;179452020
N2B	12241	36946;36947;36948	chr2:178587295;178587294;178587293	chr2:179452022;179452021;179452020
Novex-1	12366	37321;37322;37323	chr2:178587295;178587294;178587293	chr2:179452022;179452021;179452020
Novex-2	12433	37522;37523;37524	chr2:178587295;178587294;178587293	chr2:179452022;179452021;179452020
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-42
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1091
• 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
R/C	rs773942316	-1.667	1.0	N	0.898	0.46	0.590936018357	gnomAD-2.1.1	3.23E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.28818E-04	None	0	8.94E-06	0
R/C	rs773942316	-1.667	1.0	N	0.898	0.46	0.590936018357	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07727E-04	0
R/C	rs773942316	-1.667	1.0	N	0.898	0.46	0.590936018357	gnomAD-4.0.0	1.98411E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.23924E-06	2.85513E-04	1.60226E-05
R/H	rs202240487	-2.232	1.0	N	0.76	0.445	None	gnomAD-2.1.1	1.53426E-03	None	None	None	None	N	None	4.14E-05	2.84E-05	None	0	0	None	1.33041E-02	None	0	1.33578E-04	2.81532E-04
R/H	rs202240487	-2.232	1.0	N	0.76	0.445	None	gnomAD-3.1.2	5.00013E-04	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47124E-04	1.3278E-02	0
R/H	rs202240487	-2.232	1.0	N	0.76	0.445	None	1000 genomes	3.19489E-03	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1.64E-02	None
R/H	rs202240487	-2.232	1.0	N	0.76	0.445	None	gnomAD-4.0.0	9.64633E-04	None	None	None	None	N	None	6.67022E-05	6.672E-05	None	0	0	None	0	0	2.56895E-04	1.31556E-02	7.36731E-04
R/L	rs202240487	-0.935	1.0	N	0.78	0.507	0.573237765134	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
R/L	rs202240487	-0.935	1.0	N	0.78	0.507	0.573237765134	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/L	rs202240487	-0.935	1.0	N	0.78	0.507	0.573237765134	gnomAD-4.0.0	3.09994E-06	None	None	None	None	N	None	4.00855E-05	0	None	0	0	None	0	0	0	0	3.20431E-05

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
R/A	0.9854	likely_pathogenic	0.983	pathogenic	-2.339	Highly Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
R/C	0.7137	likely_pathogenic	0.6754	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.898	deleterious	N	0.470714129	None	None	N
R/D	0.9984	likely_pathogenic	0.9982	pathogenic	-0.928	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
R/E	0.9753	likely_pathogenic	0.9714	pathogenic	-0.709	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	N
R/F	0.9853	likely_pathogenic	0.9803	pathogenic	-1.579	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
R/G	0.9687	likely_pathogenic	0.9632	pathogenic	-2.673	Highly Destabilizing	1.0	D	0.78	deleterious	N	0.498604527	None	None	N
R/H	0.594	likely_pathogenic	0.5444	ambiguous	-2.353	Highly Destabilizing	1.0	D	0.76	deleterious	N	0.50684696	None	None	N
R/I	0.9753	likely_pathogenic	0.9757	pathogenic	-1.357	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
R/K	0.2961	likely_benign	0.2723	benign	-1.334	Destabilizing	0.998	D	0.459	neutral	None	None	None	None	N
R/L	0.9146	likely_pathogenic	0.9184	pathogenic	-1.357	Destabilizing	1.0	D	0.78	deleterious	N	0.488627347	None	None	N
R/M	0.921	likely_pathogenic	0.9167	pathogenic	-1.773	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
R/N	0.9937	likely_pathogenic	0.992	pathogenic	-1.307	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
R/P	0.9993	likely_pathogenic	0.9994	pathogenic	-1.677	Destabilizing	1.0	D	0.885	deleterious	D	0.532926933	None	None	N
R/Q	0.5005	ambiguous	0.4364	ambiguous	-1.248	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
R/S	0.9946	likely_pathogenic	0.9932	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.774	deleterious	N	0.477458398	None	None	N
R/T	0.988	likely_pathogenic	0.9868	pathogenic	-1.904	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
R/V	0.9786	likely_pathogenic	0.9773	pathogenic	-1.677	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
R/W	0.8497	likely_pathogenic	0.8162	pathogenic	-0.982	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
R/Y	0.948	likely_pathogenic	0.9269	pathogenic	-0.91	Destabilizing	1.0	D	0.911	deleterious	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.