TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32573	97942;97943;97944	chr2:178541360;178541359;178541358	chr2:179406087;179406086;179406085
N2AB	30932	93019;93020;93021	chr2:178541360;178541359;178541358	chr2:179406087;179406086;179406085
N2A	30005	90238;90239;90240	chr2:178541360;178541359;178541358	chr2:179406087;179406086;179406085
N2B	23508	70747;70748;70749	chr2:178541360;178541359;178541358	chr2:179406087;179406086;179406085
Novex-1	23633	71122;71123;71124	chr2:178541360;178541359;178541358	chr2:179406087;179406086;179406085
Novex-2	23700	71323;71324;71325	chr2:178541360;178541359;178541358	chr2:179406087;179406086;179406085
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: Fn3-125
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1525
• 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	rs569593251	-1.463	1.0	D	0.825	0.558	None	gnomAD-2.1.1	6.15E-05	None	None	None	None	N	None	7.09E-05	3.11E-05	None	0	0	None	2.13569E-04	None	0	4.93E-05	1.78126E-04
R/C	rs569593251	-1.463	1.0	D	0.825	0.558	None	gnomAD-3.1.2	7.89E-05	None	None	None	None	N	None	2.41E-05	0	0	0	1.92456E-04	None	0	0	7.35E-05	1.03563E-03	0
R/C	rs569593251	-1.463	1.0	D	0.825	0.558	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	2E-03	None
R/C	rs569593251	-1.463	1.0	D	0.825	0.558	None	gnomAD-4.0.0	5.88108E-05	None	None	None	None	N	None	2.67294E-05	1.71597E-05	None	0	9.05674E-05	None	1.58725E-05	0	5.37826E-05	2.14423E-04	6.46412E-05
R/H	rs776377343	-2.008	1.0	D	0.826	0.532	None	gnomAD-2.1.1	1.94E-05	None	None	None	None	N	None	4.39E-05	3.05E-05	None	0	0	None	7.15E-05	None	0	8.62E-06	0
R/H	rs776377343	-2.008	1.0	D	0.826	0.532	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/H	rs776377343	-2.008	1.0	D	0.826	0.532	None	gnomAD-4.0.0	1.7529E-05	None	None	None	None	N	None	2.6773E-05	1.72159E-05	None	0	2.26162E-05	None	0	0	1.62272E-05	4.52008E-05	1.61697E-05
R/L	None	None	1.0	N	0.732	0.548	0.646940692236	gnomAD-4.0.0	6.91943E-07	None	None	None	None	N	None	0	0	None	0	2.56279E-05	None	0	0	0	0	0
R/S	None	None	1.0	N	0.734	0.504	0.487772906946	gnomAD-4.0.0	6.91508E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06318E-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	0.9127	likely_pathogenic	0.9224	pathogenic	-2.026	Highly Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
R/C	0.3823	ambiguous	0.4026	ambiguous	-1.932	Destabilizing	1.0	D	0.825	deleterious	D	0.528068768	None	None	N
R/D	0.9934	likely_pathogenic	0.994	pathogenic	-1.027	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
R/E	0.9046	likely_pathogenic	0.911	pathogenic	-0.805	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
R/F	0.9084	likely_pathogenic	0.9164	pathogenic	-1.199	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
R/G	0.926	likely_pathogenic	0.9422	pathogenic	-2.373	Highly Destabilizing	1.0	D	0.732	prob.delet.	D	0.550692474	None	None	N
R/H	0.2474	likely_benign	0.2688	benign	-2.196	Highly Destabilizing	1.0	D	0.826	deleterious	D	0.528068768	None	None	N
R/I	0.7483	likely_pathogenic	0.7755	pathogenic	-1.015	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
R/K	0.2589	likely_benign	0.2909	benign	-1.369	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
R/L	0.7055	likely_pathogenic	0.7362	pathogenic	-1.015	Destabilizing	1.0	D	0.732	prob.delet.	N	0.514737453	None	None	N
R/M	0.7348	likely_pathogenic	0.7737	pathogenic	-1.528	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
R/N	0.968	likely_pathogenic	0.9735	pathogenic	-1.394	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
R/P	0.9986	likely_pathogenic	0.9988	pathogenic	-1.341	Destabilizing	1.0	D	0.798	deleterious	D	0.551199453	None	None	N
R/Q	0.2394	likely_benign	0.2642	benign	-1.225	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
R/S	0.9515	likely_pathogenic	0.9587	pathogenic	-2.275	Highly Destabilizing	1.0	D	0.734	prob.delet.	N	0.509378175	None	None	N
R/T	0.8604	likely_pathogenic	0.8832	pathogenic	-1.838	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
R/V	0.7916	likely_pathogenic	0.8126	pathogenic	-1.341	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
R/W	0.5465	ambiguous	0.5904	pathogenic	-0.726	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
R/Y	0.8167	likely_pathogenic	0.8394	pathogenic	-0.592	Destabilizing	1.0	D	0.831	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.