TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19025	57298;57299;57300	chr2:178598544;178598543;178598542	chr2:179463271;179463270;179463269
N2AB	17384	52375;52376;52377	chr2:178598544;178598543;178598542	chr2:179463271;179463270;179463269
N2A	16457	49594;49595;49596	chr2:178598544;178598543;178598542	chr2:179463271;179463270;179463269
N2B	9960	30103;30104;30105	chr2:178598544;178598543;178598542	chr2:179463271;179463270;179463269
Novex-1	10085	30478;30479;30480	chr2:178598544;178598543;178598542	chr2:179463271;179463270;179463269
Novex-2	10152	30679;30680;30681	chr2:178598544;178598543;178598542	chr2:179463271;179463270;179463269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-26
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1529
• 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
V/A	rs762688055	-2.808	0.058	N	0.325	0.351	0.600985507913	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	0	None	0	5.25818E-04	None	0	None	0	0	0
V/A	rs762688055	-2.808	0.058	N	0.325	0.351	0.600985507913	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	5.82298E-04	None	0	0	0	0	0
V/A	rs762688055	-2.808	0.058	N	0.325	0.351	0.600985507913	gnomAD-4.0.0	8.6995E-06	None	None	None	None	N	None	0	0	None	0	2.46615E-04	None	0	0	1.69677E-06	0	1.60421E-05
V/F	None	None	0.976	D	0.744	0.622	0.750674329801	gnomAD-4.0.0	6.8647E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6608E-05
V/I	rs181957743	-0.612	0.075	N	0.251	0.129	None	gnomAD-2.1.1	1.70452E-04	None	None	None	None	N	None	0	1.08244E-03	None	0	0	None	6.85E-05	None	0	3.93E-05	4.25653E-04
V/I	rs181957743	-0.612	0.075	N	0.251	0.129	None	gnomAD-3.1.2	1.11873E-04	None	None	None	None	N	None	2.42E-05	9.18274E-04	0	0	0	None	0	0	2.94E-05	0	0
V/I	rs181957743	-0.612	0.075	N	0.251	0.129	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
V/I	rs181957743	-0.612	0.075	N	0.251	0.129	None	gnomAD-4.0.0	5.84285E-05	None	None	None	None	N	None	1.33987E-05	1.02072E-03	None	0	2.24205E-05	None	0	1.65673E-04	1.9514E-05	5.58809E-05	4.8134E-05

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
V/A	0.5509	ambiguous	0.5983	pathogenic	-2.351	Highly Destabilizing	0.058	N	0.325	neutral	N	0.515308382	None	None	N
V/C	0.9209	likely_pathogenic	0.9308	pathogenic	-1.724	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
V/D	0.997	likely_pathogenic	0.9972	pathogenic	-3.42	Highly Destabilizing	0.971	D	0.885	deleterious	D	0.538781461	None	None	N
V/E	0.9907	likely_pathogenic	0.9895	pathogenic	-3.1	Highly Destabilizing	0.978	D	0.839	deleterious	None	None	None	None	N
V/F	0.78	likely_pathogenic	0.8115	pathogenic	-1.394	Destabilizing	0.976	D	0.744	deleterious	D	0.538527972	None	None	N
V/G	0.8962	likely_pathogenic	0.9104	pathogenic	-2.952	Highly Destabilizing	0.942	D	0.839	deleterious	D	0.538781461	None	None	N
V/H	0.9966	likely_pathogenic	0.9969	pathogenic	-2.839	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
V/I	0.0904	likely_benign	0.089	benign	-0.599	Destabilizing	0.075	N	0.251	neutral	N	0.440525024	None	None	N
V/K	0.9928	likely_pathogenic	0.992	pathogenic	-2.151	Highly Destabilizing	0.978	D	0.845	deleterious	None	None	None	None	N
V/L	0.492	ambiguous	0.4806	ambiguous	-0.599	Destabilizing	0.455	N	0.537	neutral	N	0.461116514	None	None	N
V/M	0.5999	likely_pathogenic	0.6112	pathogenic	-0.716	Destabilizing	0.956	D	0.645	neutral	None	None	None	None	N
V/N	0.9909	likely_pathogenic	0.9918	pathogenic	-2.849	Highly Destabilizing	0.993	D	0.905	deleterious	None	None	None	None	N
V/P	0.963	likely_pathogenic	0.9704	pathogenic	-1.164	Destabilizing	0.978	D	0.858	deleterious	None	None	None	None	N
V/Q	0.9867	likely_pathogenic	0.9866	pathogenic	-2.496	Highly Destabilizing	0.993	D	0.887	deleterious	None	None	None	None	N
V/R	0.985	likely_pathogenic	0.9835	pathogenic	-2.211	Highly Destabilizing	0.978	D	0.899	deleterious	None	None	None	None	N
V/S	0.9269	likely_pathogenic	0.9358	pathogenic	-3.34	Highly Destabilizing	0.915	D	0.813	deleterious	None	None	None	None	N
V/T	0.6935	likely_pathogenic	0.7141	pathogenic	-2.859	Highly Destabilizing	0.86	D	0.595	neutral	None	None	None	None	N
V/W	0.9931	likely_pathogenic	0.9937	pathogenic	-1.969	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9811	likely_pathogenic	0.9834	pathogenic	-1.617	Destabilizing	0.978	D	0.755	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.