TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26062	78409;78410;78411	chr2:178567948;178567947;178567946	chr2:179432675;179432674;179432673
N2AB	24421	73486;73487;73488	chr2:178567948;178567947;178567946	chr2:179432675;179432674;179432673
N2A	23494	70705;70706;70707	chr2:178567948;178567947;178567946	chr2:179432675;179432674;179432673
N2B	16997	51214;51215;51216	chr2:178567948;178567947;178567946	chr2:179432675;179432674;179432673
Novex-1	17122	51589;51590;51591	chr2:178567948;178567947;178567946	chr2:179432675;179432674;179432673
Novex-2	17189	51790;51791;51792	chr2:178567948;178567947;178567946	chr2:179432675;179432674;179432673
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: Fn3-77
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2517
• 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	0.557	0.325	0.405012372841	gnomAD-4.0.0	1.59178E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	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
E/A	0.5175	ambiguous	0.5795	pathogenic	-1.553	Destabilizing	0.999	D	0.659	neutral	N	0.495135033	None	None	N
E/C	0.9292	likely_pathogenic	0.931	pathogenic	-0.919	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.692	likely_pathogenic	0.7381	pathogenic	-1.649	Destabilizing	0.999	D	0.557	neutral	N	0.487666295	None	None	N
E/F	0.9602	likely_pathogenic	0.9696	pathogenic	-1.201	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/G	0.7374	likely_pathogenic	0.803	pathogenic	-1.976	Destabilizing	1.0	D	0.687	prob.neutral	N	0.517544929	None	None	N
E/H	0.9227	likely_pathogenic	0.9373	pathogenic	-1.272	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/I	0.7187	likely_pathogenic	0.765	pathogenic	-0.344	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/K	0.83	likely_pathogenic	0.8694	pathogenic	-1.611	Destabilizing	0.999	D	0.607	neutral	N	0.47494041	None	None	N
E/L	0.8441	likely_pathogenic	0.8805	pathogenic	-0.344	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/M	0.7774	likely_pathogenic	0.8076	pathogenic	0.448	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/N	0.8399	likely_pathogenic	0.8764	pathogenic	-1.911	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/P	0.9987	likely_pathogenic	0.999	pathogenic	-0.731	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/Q	0.346	ambiguous	0.3741	ambiguous	-1.592	Destabilizing	1.0	D	0.678	prob.neutral	N	0.468015483	None	None	N
E/R	0.8711	likely_pathogenic	0.8987	pathogenic	-1.443	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/S	0.5747	likely_pathogenic	0.6319	pathogenic	-2.582	Highly Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/T	0.6276	likely_pathogenic	0.6898	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/V	0.5696	likely_pathogenic	0.6126	pathogenic	-0.731	Destabilizing	1.0	D	0.681	prob.neutral	N	0.473712642	None	None	N
E/W	0.9931	likely_pathogenic	0.9947	pathogenic	-1.243	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.9469	likely_pathogenic	0.9583	pathogenic	-1.027	Destabilizing	1.0	D	0.735	prob.delet.	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.