TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21118	63577;63578;63579	chr2:178588055;178588054;178588053	chr2:179452782;179452781;179452780
N2AB	19477	58654;58655;58656	chr2:178588055;178588054;178588053	chr2:179452782;179452781;179452780
N2A	18550	55873;55874;55875	chr2:178588055;178588054;178588053	chr2:179452782;179452781;179452780
N2B	12053	36382;36383;36384	chr2:178588055;178588054;178588053	chr2:179452782;179452781;179452780
Novex-1	12178	36757;36758;36759	chr2:178588055;178588054;178588053	chr2:179452782;179452781;179452780
Novex-2	12245	36958;36959;36960	chr2:178588055;178588054;178588053	chr2:179452782;179452781;179452780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-41
• Domain position: 55
• Structural Position: 67
• Q(SASA): 0.358
• 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/G	None	None	0.996	N	0.608	0.416	0.593399868425	gnomAD-4.0.0	6.84526E-07	None	None	None	None	N	None	2.99115E-05	0	None	0	0	None	0	0	0	0	0
R/Q	rs755796313	-0.256	0.999	N	0.624	0.314	0.223847106136	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.92E-06	0
R/Q	rs755796313	-0.256	0.999	N	0.624	0.314	0.223847106136	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07469E-04	0
R/Q	rs755796313	-0.256	0.999	N	0.624	0.314	0.223847106136	gnomAD-4.0.0	1.11605E-05	None	None	None	None	N	None	0	0	None	3.38089E-05	0	None	0	0	1.27188E-05	2.19703E-05	0
R/W	rs200726948	-0.371	1.0	N	0.715	0.491	0.433600339574	gnomAD-2.1.1	2.90054E-04	None	None	None	None	N	None	2.06868E-04	2.83E-05	None	0	1.44928E-03	None	2.61575E-04	None	7.99936E-04	1.01988E-04	8.43882E-04
R/W	rs200726948	-0.371	1.0	N	0.715	0.491	0.433600339574	gnomAD-3.1.2	1.77695E-04	None	None	None	None	N	None	1.44942E-04	0	0	0	1.55642E-03	None	4.70987E-04	0	1.03011E-04	2.07469E-04	0
R/W	rs200726948	-0.371	1.0	N	0.715	0.491	0.433600339574	gnomAD-4.0.0	1.7113E-04	None	None	None	None	N	None	1.60368E-04	3.3379E-05	None	0	1.29795E-03	None	9.06278E-04	4.94071E-04	7.7161E-05	3.73479E-04	2.88341E-04

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	0.6078	likely_pathogenic	0.4953	ambiguous	-0.598	Destabilizing	0.983	D	0.537	neutral	None	None	None	None	N
R/C	0.3244	likely_benign	0.2546	benign	-0.476	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/D	0.8954	likely_pathogenic	0.8454	pathogenic	-0.116	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
R/E	0.6202	likely_pathogenic	0.5283	ambiguous	-0.016	Destabilizing	0.983	D	0.472	neutral	None	None	None	None	N
R/F	0.731	likely_pathogenic	0.645	pathogenic	-0.585	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
R/G	0.5785	likely_pathogenic	0.4841	ambiguous	-0.883	Destabilizing	0.996	D	0.608	neutral	N	0.466279903	None	None	N
R/H	0.2053	likely_benign	0.1704	benign	-1.29	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
R/I	0.3543	ambiguous	0.2846	benign	0.154	Stabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
R/K	0.1396	likely_benign	0.1199	benign	-0.665	Destabilizing	0.437	N	0.209	neutral	None	None	None	None	N
R/L	0.3399	likely_benign	0.2703	benign	0.154	Stabilizing	0.996	D	0.608	neutral	N	0.489313475	None	None	N
R/M	0.4462	ambiguous	0.3545	ambiguous	-0.088	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
R/N	0.814	likely_pathogenic	0.728	pathogenic	-0.108	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	N
R/P	0.4651	ambiguous	0.3372	benign	-0.075	Destabilizing	1.0	D	0.739	prob.delet.	N	0.484483658	None	None	N
R/Q	0.1687	likely_benign	0.1365	benign	-0.307	Destabilizing	0.999	D	0.624	neutral	N	0.500490474	None	None	N
R/S	0.7654	likely_pathogenic	0.6652	pathogenic	-0.774	Destabilizing	0.983	D	0.63	neutral	None	None	None	None	N
R/T	0.4777	ambiguous	0.3672	ambiguous	-0.506	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
R/V	0.4468	ambiguous	0.3658	ambiguous	-0.075	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
R/W	0.33	likely_benign	0.2713	benign	-0.335	Destabilizing	1.0	D	0.715	prob.delet.	N	0.503880765	None	None	N
R/Y	0.5708	likely_pathogenic	0.478	ambiguous	-0.008	Destabilizing	0.999	D	0.736	prob.delet.	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.