TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18846	56761;56762;56763	chr2:178599257;178599256;178599255	chr2:179463984;179463983;179463982
N2AB	17205	51838;51839;51840	chr2:178599257;178599256;178599255	chr2:179463984;179463983;179463982
N2A	16278	49057;49058;49059	chr2:178599257;178599256;178599255	chr2:179463984;179463983;179463982
N2B	9781	29566;29567;29568	chr2:178599257;178599256;178599255	chr2:179463984;179463983;179463982
Novex-1	9906	29941;29942;29943	chr2:178599257;178599256;178599255	chr2:179463984;179463983;179463982
Novex-2	9973	30142;30143;30144	chr2:178599257;178599256;178599255	chr2:179463984;179463983;179463982
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-24
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0706
• 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
I/T	rs766906652	-3.42	0.124	N	0.794	0.299	None	gnomAD-2.1.1	1.46E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.03E-05	2.0903E-04
I/T	rs766906652	-3.42	0.124	N	0.794	0.299	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
I/T	rs766906652	-3.42	0.124	N	0.794	0.299	None	gnomAD-4.0.0	2.17298E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.84042E-05	0	1.6575E-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
I/A	0.7658	likely_pathogenic	0.7158	pathogenic	-2.571	Highly Destabilizing	0.072	N	0.75	deleterious	None	None	None	None	N
I/C	0.8746	likely_pathogenic	0.8215	pathogenic	-1.961	Destabilizing	0.909	D	0.827	deleterious	None	None	None	None	N
I/D	0.9921	likely_pathogenic	0.9906	pathogenic	-3.45	Highly Destabilizing	0.726	D	0.871	deleterious	None	None	None	None	N
I/E	0.9841	likely_pathogenic	0.9814	pathogenic	-3.145	Highly Destabilizing	0.726	D	0.854	deleterious	None	None	None	None	N
I/F	0.4738	ambiguous	0.4764	ambiguous	-1.595	Destabilizing	0.497	N	0.739	prob.delet.	N	0.500530546	None	None	N
I/G	0.9756	likely_pathogenic	0.9654	pathogenic	-3.166	Highly Destabilizing	0.726	D	0.835	deleterious	None	None	None	None	N
I/H	0.9689	likely_pathogenic	0.9591	pathogenic	-2.869	Highly Destabilizing	0.968	D	0.866	deleterious	None	None	None	None	N
I/K	0.9778	likely_pathogenic	0.9701	pathogenic	-2.223	Highly Destabilizing	0.726	D	0.859	deleterious	None	None	None	None	N
I/L	0.2239	likely_benign	0.2307	benign	-0.799	Destabilizing	0.025	N	0.39	neutral	N	0.46362281	None	None	N
I/M	0.2937	likely_benign	0.2737	benign	-0.87	Destabilizing	0.497	N	0.697	prob.neutral	N	0.511673047	None	None	N
I/N	0.903	likely_pathogenic	0.8824	pathogenic	-2.87	Highly Destabilizing	0.859	D	0.867	deleterious	N	0.487212223	None	None	N
I/P	0.9719	likely_pathogenic	0.9703	pathogenic	-1.377	Destabilizing	0.89	D	0.873	deleterious	None	None	None	None	N
I/Q	0.9692	likely_pathogenic	0.9594	pathogenic	-2.568	Highly Destabilizing	0.89	D	0.872	deleterious	None	None	None	None	N
I/R	0.9651	likely_pathogenic	0.953	pathogenic	-2.197	Highly Destabilizing	0.726	D	0.87	deleterious	None	None	None	None	N
I/S	0.8563	likely_pathogenic	0.82	pathogenic	-3.448	Highly Destabilizing	0.497	N	0.821	deleterious	D	0.525679707	None	None	N
I/T	0.8025	likely_pathogenic	0.7485	pathogenic	-2.975	Highly Destabilizing	0.124	N	0.794	deleterious	N	0.514809352	None	None	N
I/V	0.074	likely_benign	0.0667	benign	-1.377	Destabilizing	None	N	0.213	neutral	N	0.362767956	None	None	N
I/W	0.9848	likely_pathogenic	0.9824	pathogenic	-2.059	Highly Destabilizing	0.968	D	0.85	deleterious	None	None	None	None	N
I/Y	0.9223	likely_pathogenic	0.9094	pathogenic	-1.753	Destabilizing	0.726	D	0.834	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.