TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27208	81847;81848;81849	chr2:178564510;178564509;178564508	chr2:179429237;179429236;179429235
N2AB	25567	76924;76925;76926	chr2:178564510;178564509;178564508	chr2:179429237;179429236;179429235
N2A	24640	74143;74144;74145	chr2:178564510;178564509;178564508	chr2:179429237;179429236;179429235
N2B	18143	54652;54653;54654	chr2:178564510;178564509;178564508	chr2:179429237;179429236;179429235
Novex-1	18268	55027;55028;55029	chr2:178564510;178564509;178564508	chr2:179429237;179429236;179429235
Novex-2	18335	55228;55229;55230	chr2:178564510;178564509;178564508	chr2:179429237;179429236;179429235
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-86
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.132
• 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
E/D	None	None	0.999	N	0.657	0.349	0.353548585375	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
E/K	None	None	0.999	D	0.68	0.446	0.461845970543	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
E/A	0.9665	likely_pathogenic	0.9508	pathogenic	-1.797	Destabilizing	0.999	D	0.689	prob.neutral	D	0.545395647	None	None	N
E/C	0.9925	likely_pathogenic	0.9919	pathogenic	-0.989	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.9802	likely_pathogenic	0.9772	pathogenic	-1.894	Destabilizing	0.999	D	0.657	neutral	N	0.502198925	None	None	N
E/F	0.9967	likely_pathogenic	0.9958	pathogenic	-1.483	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.9809	likely_pathogenic	0.9741	pathogenic	-2.174	Highly Destabilizing	1.0	D	0.744	deleterious	D	0.547170074	None	None	N
E/H	0.9935	likely_pathogenic	0.9913	pathogenic	-1.356	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/I	0.9877	likely_pathogenic	0.9829	pathogenic	-0.704	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/K	0.9763	likely_pathogenic	0.9672	pathogenic	-1.844	Destabilizing	0.999	D	0.68	prob.neutral	D	0.53738025	None	None	N
E/L	0.9843	likely_pathogenic	0.9788	pathogenic	-0.704	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/M	0.9829	likely_pathogenic	0.9748	pathogenic	0.05	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.9958	likely_pathogenic	0.9942	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.056	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/Q	0.8365	likely_pathogenic	0.7844	pathogenic	-1.737	Destabilizing	1.0	D	0.759	deleterious	N	0.478116734	None	None	N
E/R	0.9834	likely_pathogenic	0.9787	pathogenic	-1.628	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/S	0.9808	likely_pathogenic	0.9719	pathogenic	-2.663	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/T	0.9891	likely_pathogenic	0.9835	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/V	0.9727	likely_pathogenic	0.9603	pathogenic	-1.056	Destabilizing	1.0	D	0.739	prob.delet.	D	0.53479981	None	None	N
E/W	0.9982	likely_pathogenic	0.9982	pathogenic	-1.571	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9941	likely_pathogenic	0.9929	pathogenic	-1.326	Destabilizing	1.0	D	0.772	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.