TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28118	84577;84578;84579	chr2:178561780;178561779;178561778	chr2:179426507;179426506;179426505
N2AB	26477	79654;79655;79656	chr2:178561780;178561779;178561778	chr2:179426507;179426506;179426505
N2A	25550	76873;76874;76875	chr2:178561780;178561779;178561778	chr2:179426507;179426506;179426505
N2B	19053	57382;57383;57384	chr2:178561780;178561779;178561778	chr2:179426507;179426506;179426505
Novex-1	19178	57757;57758;57759	chr2:178561780;178561779;178561778	chr2:179426507;179426506;179426505
Novex-2	19245	57958;57959;57960	chr2:178561780;178561779;178561778	chr2:179426507;179426506;179426505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-92
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.8932
• 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	rs56057221	-0.279	1.0	N	0.65	0.371	None	gnomAD-2.1.1	6.02293E-03	None	None	None	None	I	None	6.4408E-02	2.40766E-03	None	0	0	None	3.92336E-04	None	4E-05	1.33243E-04	1.5493E-03
R/C	rs56057221	-0.279	1.0	N	0.65	0.371	None	gnomAD-3.1.2	1.80138E-02	None	None	None	None	I	None	6.32456E-02	4.97969E-03	0	0	0	None	0	3.16456E-03	2.49919E-04	6.21633E-04	1.14723E-02
R/C	rs56057221	-0.279	1.0	N	0.65	0.371	None	1000 genomes	1.61741E-02	None	None	None	None	I	None	5.67E-02	8.6E-03	None	None	0	0	None	None	None	0	None
R/C	rs56057221	-0.279	1.0	N	0.65	0.371	None	gnomAD-4.0.0	3.41543E-03	None	None	None	None	I	None	6.51652E-02	3.36712E-03	None	0	4.46867E-05	None	1.56274E-05	1.81638E-03	7.62893E-05	3.07469E-04	4.64163E-03
R/G	None	None	0.998	N	0.544	0.3	0.365509141856	gnomAD-4.0.0	3.42152E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49759E-06	0	0
R/H	rs72648220	-0.514	1.0	N	0.585	0.299	0.273938319068	gnomAD-2.1.1	3.63E-05	None	None	None	None	I	None	0	8.71E-05	None	0	5.6E-05	None	0	None	0	4.46E-05	0
R/H	rs72648220	-0.514	1.0	N	0.585	0.299	0.273938319068	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	7.24E-05	1.3101E-04	0	0	0	None	0	0	4.41E-05	0	0
R/H	rs72648220	-0.514	1.0	N	0.585	0.299	0.273938319068	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/H	rs72648220	-0.514	1.0	N	0.585	0.299	0.273938319068	Begay (2015)	None	DCM	het	None	None	I	WGS prioritisation; filtering with ANNOVAR; co-segregates within family (n = 2, 2 affected (total 2))	None	None	None	None	None	None	None	None	None	None	None
R/H	rs72648220	-0.514	1.0	N	0.585	0.299	0.273938319068	gnomAD-4.0.0	1.85924E-05	None	None	None	None	I	None	5.33248E-05	1.0001E-04	None	0	0	None	0	0	1.61057E-05	0	1.60082E-05
R/L	rs72648220	0.319	0.998	N	0.544	0.324	None	gnomAD-2.1.1	2.15E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	4.7E-05	0
R/L	rs72648220	0.319	0.998	N	0.544	0.324	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
R/L	rs72648220	0.319	0.998	N	0.544	0.324	None	gnomAD-4.0.0	1.23959E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69533E-05	0	0
R/P	None	None	1.0	N	0.591	0.34	0.37550373646	gnomAD-4.0.0	6.84312E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99526E-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
R/A	0.5464	ambiguous	0.5701	pathogenic	0.058	Stabilizing	0.992	D	0.542	neutral	None	None	None	None	I
R/C	0.1977	likely_benign	0.2676	benign	-0.271	Destabilizing	1.0	D	0.65	neutral	N	0.500558948	None	None	I
R/D	0.6954	likely_pathogenic	0.6927	pathogenic	-0.359	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	I
R/E	0.5587	ambiguous	0.5676	pathogenic	-0.314	Destabilizing	0.992	D	0.562	neutral	None	None	None	None	I
R/F	0.7076	likely_pathogenic	0.7163	pathogenic	-0.247	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
R/G	0.2262	likely_benign	0.2374	benign	-0.085	Destabilizing	0.998	D	0.544	neutral	N	0.420981179	None	None	I
R/H	0.0963	likely_benign	0.0946	benign	-0.58	Destabilizing	1.0	D	0.585	neutral	N	0.467362178	None	None	I
R/I	0.6362	likely_pathogenic	0.6774	pathogenic	0.391	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	I
R/K	0.1335	likely_benign	0.1305	benign	-0.179	Destabilizing	0.611	D	0.249	neutral	None	None	None	None	I
R/L	0.4121	ambiguous	0.4346	ambiguous	0.391	Stabilizing	0.998	D	0.544	neutral	N	0.488949153	None	None	I
R/M	0.4946	ambiguous	0.5174	ambiguous	-0.094	Destabilizing	1.0	D	0.538	neutral	None	None	None	None	I
R/N	0.5287	ambiguous	0.5166	ambiguous	-0.125	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	I
R/P	0.692	likely_pathogenic	0.6796	pathogenic	0.298	Stabilizing	1.0	D	0.591	neutral	N	0.463501064	None	None	I
R/Q	0.1372	likely_benign	0.1379	benign	-0.146	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	I
R/S	0.5351	ambiguous	0.5515	ambiguous	-0.276	Destabilizing	0.996	D	0.599	neutral	N	0.474858524	None	None	I
R/T	0.4593	ambiguous	0.48	ambiguous	-0.124	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	I
R/V	0.6943	likely_pathogenic	0.727	pathogenic	0.298	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	I
R/W	0.2593	likely_benign	0.2587	benign	-0.438	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
R/Y	0.4678	ambiguous	0.4631	ambiguous	-0.032	Destabilizing	1.0	D	0.589	neutral	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.