TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15908	47947;47948;47949	chr2:178617363;178617362;178617361	chr2:179482090;179482089;179482088
N2AB	14267	43024;43025;43026	chr2:178617363;178617362;178617361	chr2:179482090;179482089;179482088
N2A	13340	40243;40244;40245	chr2:178617363;178617362;178617361	chr2:179482090;179482089;179482088
N2B	6843	20752;20753;20754	chr2:178617363;178617362;178617361	chr2:179482090;179482089;179482088
Novex-1	6968	21127;21128;21129	chr2:178617363;178617362;178617361	chr2:179482090;179482089;179482088
Novex-2	7035	21328;21329;21330	chr2:178617363;178617362;178617361	chr2:179482090;179482089;179482088
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: Fn3-3
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.253
• Predicted PPI site: I

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	rs767724702	-0.554	1.0	D	0.745	0.427	0.792423958598	gnomAD-2.1.1	9.38E-06	None	None	None	None	I	None	0	0	None	0	6.4E-05	None	0	None	0	1.02E-05	0
R/C	rs767724702	-0.554	1.0	D	0.745	0.427	0.792423958598	gnomAD-4.0.0	5.58773E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.26823E-06	0	0
R/H	rs72677237	-1.517	1.0	N	0.805	0.368	None	gnomAD-2.1.1	6.46738E-03	None	None	None	None	I	None	1.11329E-03	4.76737E-03	None	2.40035E-02	0	None	1.08364E-02	None	1.80596E-03	7.38292E-03	1.01587E-02
R/H	rs72677237	-1.517	1.0	N	0.805	0.368	None	gnomAD-3.1.2	5.39843E-03	None	None	None	None	I	None	1.44955E-03	4.39402E-03	0	2.74091E-02	0	None	1.88253E-03	2.8481E-02	7.52755E-03	8.07119E-03	9.10834E-03
R/H	rs72677237	-1.517	1.0	N	0.805	0.368	None	1000 genomes	2.99521E-03	None	None	None	None	I	None	8E-04	8.6E-03	None	None	0	6E-03	None	None	None	2E-03	None
R/H	rs72677237	-1.517	1.0	N	0.805	0.368	None	gnomAD-4.0.0	6.40655E-03	None	None	None	None	I	None	1.49803E-03	4.87999E-03	None	2.6441E-02	0	None	2.57781E-03	1.52327E-02	6.27491E-03	1.08391E-02	8.45383E-03
R/P	None	None	1.0	N	0.746	0.38	0.630571860293	gnomAD-4.0.0	6.98924E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.76056E-04	0	0	0
R/S	rs767724702	-0.967	1.0	N	0.734	0.356	0.548188646194	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14863E-04	0	None	0	0	None	0	None	0	0	0
R/S	rs767724702	-0.967	1.0	N	0.734	0.356	0.548188646194	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/S	rs767724702	-0.967	1.0	N	0.734	0.356	0.548188646194	gnomAD-4.0.0	5.68354E-06	None	None	None	None	I	None	1.36307E-05	0	None	0	0	None	0	0	6.846E-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
R/A	0.7843	likely_pathogenic	0.7961	pathogenic	-0.858	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
R/C	0.3762	ambiguous	0.3661	ambiguous	-0.822	Destabilizing	1.0	D	0.745	deleterious	D	0.614117672	None	None	I
R/D	0.9573	likely_pathogenic	0.9606	pathogenic	-0.091	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
R/E	0.8013	likely_pathogenic	0.7967	pathogenic	0.033	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
R/F	0.8783	likely_pathogenic	0.8894	pathogenic	-0.695	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
R/G	0.7962	likely_pathogenic	0.8064	pathogenic	-1.171	Destabilizing	1.0	D	0.665	neutral	N	0.477129663	None	None	I
R/H	0.2943	likely_benign	0.2752	benign	-1.419	Destabilizing	1.0	D	0.805	deleterious	N	0.512279679	None	None	I
R/I	0.5661	likely_pathogenic	0.541	ambiguous	-0.018	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
R/K	0.2281	likely_benign	0.2582	benign	-0.906	Destabilizing	0.998	D	0.556	neutral	None	None	None	None	I
R/L	0.5082	ambiguous	0.504	ambiguous	-0.018	Destabilizing	1.0	D	0.665	neutral	N	0.473830233	None	None	I
R/M	0.6929	likely_pathogenic	0.698	pathogenic	-0.334	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
R/N	0.904	likely_pathogenic	0.9095	pathogenic	-0.354	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
R/P	0.6583	likely_pathogenic	0.634	pathogenic	-0.278	Destabilizing	1.0	D	0.746	deleterious	N	0.4803224	None	None	I
R/Q	0.2461	likely_benign	0.2466	benign	-0.525	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
R/S	0.874	likely_pathogenic	0.8854	pathogenic	-1.142	Destabilizing	1.0	D	0.734	prob.delet.	N	0.477214922	None	None	I
R/T	0.6571	likely_pathogenic	0.6881	pathogenic	-0.836	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
R/V	0.6767	likely_pathogenic	0.6752	pathogenic	-0.278	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
R/W	0.4734	ambiguous	0.4883	ambiguous	-0.333	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
R/Y	0.7543	likely_pathogenic	0.7662	pathogenic	-0.045	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I

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.