TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26507	79744;79745;79746	chr2:178566613;178566612;178566611	chr2:179431340;179431339;179431338
N2AB	24866	74821;74822;74823	chr2:178566613;178566612;178566611	chr2:179431340;179431339;179431338
N2A	23939	72040;72041;72042	chr2:178566613;178566612;178566611	chr2:179431340;179431339;179431338
N2B	17442	52549;52550;52551	chr2:178566613;178566612;178566611	chr2:179431340;179431339;179431338
Novex-1	17567	52924;52925;52926	chr2:178566613;178566612;178566611	chr2:179431340;179431339;179431338
Novex-2	17634	53125;53126;53127	chr2:178566613;178566612;178566611	chr2:179431340;179431339;179431338
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-81
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1606
• 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
A/D	rs538057461	-2.199	0.782	N	0.679	0.266	0.508046185061	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	5.66E-05	None	0	0	None	0	None	0	0	1.40607E-04
A/D	rs538057461	-2.199	0.782	N	0.679	0.266	0.508046185061	gnomAD-3.1.2	7.89E-05	None	None	None	None	N	None	0	7.87092E-04	0	0	0	None	0	0	0	0	0
A/D	rs538057461	-2.199	0.782	N	0.679	0.266	0.508046185061	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
A/D	rs538057461	-2.199	0.782	N	0.679	0.266	0.508046185061	gnomAD-4.0.0	2.69459E-05	None	None	None	None	N	None	0	2.88145E-04	None	0	0	None	0	0	0	0	1.13766E-04
A/S	None	None	0.038	N	0.481	0.056	0.0954503805726	gnomAD-4.0.0	1.36955E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79906E-06	0	0
A/T	rs554718474	-0.83	0.007	N	0.456	0.065	0.146414634003	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	5.66E-05	None	0	0	None	0	None	0	7.83E-06	1.40647E-04
A/T	rs554718474	-0.83	0.007	N	0.456	0.065	0.146414634003	gnomAD-3.1.2	7.89E-05	None	None	None	None	N	None	0	7.86885E-04	0	0	0	None	0	0	0	0	0
A/T	rs554718474	-0.83	0.007	N	0.456	0.065	0.146414634003	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
A/T	rs554718474	-0.83	0.007	N	0.456	0.065	0.146414634003	gnomAD-4.0.0	1.55037E-05	None	None	None	None	N	None	0	2.8339E-04	None	0	0	None	0	0	3.39075E-06	0	6.40451E-05
A/V	rs538057461	0.57	0.007	N	0.437	0.163	0.298403945805	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
A/V	rs538057461	0.57	0.007	N	0.437	0.163	0.298403945805	gnomAD-4.0.0	1.59444E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85891E-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
A/C	0.3043	likely_benign	0.2935	benign	-1.043	Destabilizing	0.973	D	0.629	neutral	None	None	None	None	N
A/D	0.4671	ambiguous	0.3925	ambiguous	-2.585	Highly Destabilizing	0.782	D	0.679	prob.neutral	N	0.482307016	None	None	N
A/E	0.3519	ambiguous	0.3067	benign	-2.428	Highly Destabilizing	0.826	D	0.675	prob.neutral	None	None	None	None	N
A/F	0.3018	likely_benign	0.2457	benign	-0.785	Destabilizing	0.906	D	0.745	deleterious	None	None	None	None	N
A/G	0.099	likely_benign	0.1022	benign	-1.51	Destabilizing	0.003	N	0.493	neutral	N	0.475960176	None	None	N
A/H	0.4877	ambiguous	0.4446	ambiguous	-2.108	Highly Destabilizing	0.991	D	0.732	prob.delet.	None	None	None	None	N
A/I	0.2251	likely_benign	0.169	benign	0.041	Stabilizing	0.704	D	0.675	neutral	None	None	None	None	N
A/K	0.5778	likely_pathogenic	0.5086	ambiguous	-1.362	Destabilizing	0.826	D	0.676	prob.neutral	None	None	None	None	N
A/L	0.1649	likely_benign	0.1353	benign	0.041	Stabilizing	0.404	N	0.61	neutral	None	None	None	None	N
A/M	0.2048	likely_benign	0.1643	benign	-0.052	Destabilizing	0.973	D	0.696	prob.neutral	None	None	None	None	N
A/N	0.2706	likely_benign	0.2234	benign	-1.56	Destabilizing	0.826	D	0.687	prob.neutral	None	None	None	None	N
A/P	0.884	likely_pathogenic	0.8613	pathogenic	-0.293	Destabilizing	0.879	D	0.695	prob.neutral	N	0.498462715	None	None	N
A/Q	0.3526	ambiguous	0.323	benign	-1.419	Destabilizing	0.906	D	0.708	prob.delet.	None	None	None	None	N
A/R	0.5026	ambiguous	0.4463	ambiguous	-1.36	Destabilizing	0.826	D	0.693	prob.neutral	None	None	None	None	N
A/S	0.0821	likely_benign	0.079	benign	-1.869	Destabilizing	0.038	N	0.481	neutral	N	0.414655427	None	None	N
A/T	0.084	likely_benign	0.0765	benign	-1.613	Destabilizing	0.007	N	0.456	neutral	N	0.473879876	None	None	N
A/V	0.136	likely_benign	0.1088	benign	-0.293	Destabilizing	0.007	N	0.437	neutral	N	0.519847026	None	None	N
A/W	0.7128	likely_pathogenic	0.6829	pathogenic	-1.645	Destabilizing	0.991	D	0.789	deleterious	None	None	None	None	N
A/Y	0.4276	ambiguous	0.3834	ambiguous	-1.094	Destabilizing	0.906	D	0.747	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.