TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25584	76975;76976;76977	chr2:178569382;178569381;178569380	chr2:179434109;179434108;179434107
N2AB	23943	72052;72053;72054	chr2:178569382;178569381;178569380	chr2:179434109;179434108;179434107
N2A	23016	69271;69272;69273	chr2:178569382;178569381;178569380	chr2:179434109;179434108;179434107
N2B	16519	49780;49781;49782	chr2:178569382;178569381;178569380	chr2:179434109;179434108;179434107
Novex-1	16644	50155;50156;50157	chr2:178569382;178569381;178569380	chr2:179434109;179434108;179434107
Novex-2	16711	50356;50357;50358	chr2:178569382;178569381;178569380	chr2:179434109;179434108;179434107
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: Ig-135
• Domain position: 71
• Structural Position: 159
• Q(SASA): 0.4722
• 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/K	rs1217257725	0.372	0.928	N	0.634	0.347	0.394990421082	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/K	rs1217257725	0.372	0.928	N	0.634	0.347	0.394990421082	gnomAD-4.0.0	2.73746E-06	None	None	None	None	N	None	0	0	None	0	7.56506E-05	None	0	0	8.99616E-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
E/A	0.2294	likely_benign	0.2471	benign	-0.556	Destabilizing	0.928	D	0.671	neutral	D	0.524458704	None	None	N
E/C	0.8432	likely_pathogenic	0.8582	pathogenic	0.032	Stabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
E/D	0.3585	ambiguous	0.36	ambiguous	-0.716	Destabilizing	0.039	N	0.284	neutral	N	0.495633964	None	None	N
E/F	0.8727	likely_pathogenic	0.8873	pathogenic	-0.638	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
E/G	0.3419	ambiguous	0.3595	ambiguous	-0.797	Destabilizing	0.978	D	0.74	deleterious	N	0.503142383	None	None	N
E/H	0.5585	ambiguous	0.5797	pathogenic	-0.844	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/I	0.4217	ambiguous	0.4373	ambiguous	0.058	Stabilizing	0.992	D	0.798	deleterious	None	None	None	None	N
E/K	0.2056	likely_benign	0.2166	benign	0.099	Stabilizing	0.928	D	0.634	neutral	N	0.507449024	None	None	N
E/L	0.5616	ambiguous	0.5933	pathogenic	0.058	Stabilizing	0.992	D	0.777	deleterious	None	None	None	None	N
E/M	0.5177	ambiguous	0.5482	ambiguous	0.467	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/N	0.4433	ambiguous	0.4518	ambiguous	-0.162	Destabilizing	0.968	D	0.75	deleterious	None	None	None	None	N
E/P	0.9909	likely_pathogenic	0.992	pathogenic	-0.126	Destabilizing	0.992	D	0.752	deleterious	None	None	None	None	N
E/Q	0.1171	likely_benign	0.1252	benign	-0.145	Destabilizing	0.978	D	0.695	prob.neutral	N	0.488125546	None	None	N
E/R	0.3589	ambiguous	0.384	ambiguous	0.112	Stabilizing	0.992	D	0.771	deleterious	None	None	None	None	N
E/S	0.2703	likely_benign	0.2851	benign	-0.365	Destabilizing	0.944	D	0.673	neutral	None	None	None	None	N
E/T	0.2286	likely_benign	0.2377	benign	-0.17	Destabilizing	0.983	D	0.719	prob.delet.	None	None	None	None	N
E/V	0.2341	likely_benign	0.2441	benign	-0.126	Destabilizing	0.989	D	0.772	deleterious	N	0.487809605	None	None	N
E/W	0.9548	likely_pathogenic	0.9598	pathogenic	-0.54	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
E/Y	0.8157	likely_pathogenic	0.8343	pathogenic	-0.398	Destabilizing	0.999	D	0.78	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.