TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5523	16792;16793;16794	chr2:178732494;178732493;178732492	chr2:179597221;179597220;179597219
N2AB	5206	15841;15842;15843	chr2:178732494;178732493;178732492	chr2:179597221;179597220;179597219
N2A	4279	13060;13061;13062	chr2:178732494;178732493;178732492	chr2:179597221;179597220;179597219
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-38
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3951
• 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
K/E	rs755764408	-0.569	0.055	N	0.545	0.199	0.276898752692	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
K/E	rs755764408	-0.569	0.055	N	0.545	0.199	0.276898752692	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	2.77485E-05	None	0	0	0	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
K/A	0.2737	likely_benign	0.2936	benign	-1.093	Destabilizing	0.157	N	0.639	neutral	None	None	None	None	N
K/C	0.5972	likely_pathogenic	0.6129	pathogenic	-1.177	Destabilizing	0.968	D	0.744	deleterious	None	None	None	None	N
K/D	0.6276	likely_pathogenic	0.6684	pathogenic	-0.83	Destabilizing	0.272	N	0.653	neutral	None	None	None	None	N
K/E	0.1244	likely_benign	0.1396	benign	-0.616	Destabilizing	0.055	N	0.545	neutral	N	0.455137478	None	None	N
K/F	0.6058	likely_pathogenic	0.6172	pathogenic	-0.45	Destabilizing	0.89	D	0.767	deleterious	None	None	None	None	N
K/G	0.5462	ambiguous	0.5748	pathogenic	-1.542	Destabilizing	0.272	N	0.722	prob.delet.	None	None	None	None	N
K/H	0.2285	likely_benign	0.2362	benign	-1.714	Destabilizing	0.567	D	0.714	prob.delet.	None	None	None	None	N
K/I	0.1959	likely_benign	0.2061	benign	0.135	Stabilizing	0.667	D	0.769	deleterious	N	0.440285456	None	None	N
K/L	0.2405	likely_benign	0.249	benign	0.135	Stabilizing	0.272	N	0.722	prob.delet.	None	None	None	None	N
K/M	0.139	likely_benign	0.1442	benign	-0.133	Destabilizing	0.726	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.3878	ambiguous	0.4219	ambiguous	-1.205	Destabilizing	0.22	N	0.572	neutral	N	0.501525916	None	None	N
K/P	0.9701	likely_pathogenic	0.9744	pathogenic	-0.248	Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	N
K/Q	0.0969	likely_benign	0.0996	benign	-1.072	Destabilizing	None	N	0.343	neutral	N	0.435146208	None	None	N
K/R	0.075	likely_benign	0.0743	benign	-0.946	Destabilizing	0.124	N	0.532	neutral	N	0.45001966	None	None	N
K/S	0.3261	likely_benign	0.347	ambiguous	-1.871	Destabilizing	0.157	N	0.562	neutral	None	None	None	None	N
K/T	0.1143	likely_benign	0.12	benign	-1.415	Destabilizing	0.22	N	0.673	neutral	N	0.442496255	None	None	N
K/V	0.1846	likely_benign	0.1947	benign	-0.248	Destabilizing	0.567	D	0.765	deleterious	None	None	None	None	N
K/W	0.669	likely_pathogenic	0.687	pathogenic	-0.369	Destabilizing	0.968	D	0.748	deleterious	None	None	None	None	N
K/Y	0.5163	ambiguous	0.5367	ambiguous	-0.056	Destabilizing	0.726	D	0.769	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.