TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21598	65017;65018;65019	chr2:178584849;178584848;178584847	chr2:179449576;179449575;179449574
N2AB	19957	60094;60095;60096	chr2:178584849;178584848;178584847	chr2:179449576;179449575;179449574
N2A	19030	57313;57314;57315	chr2:178584849;178584848;178584847	chr2:179449576;179449575;179449574
N2B	12533	37822;37823;37824	chr2:178584849;178584848;178584847	chr2:179449576;179449575;179449574
Novex-1	12658	38197;38198;38199	chr2:178584849;178584848;178584847	chr2:179449576;179449575;179449574
Novex-2	12725	38398;38399;38400	chr2:178584849;178584848;178584847	chr2:179449576;179449575;179449574
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-44
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.1462
• 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/G	rs1310732379	-2.663	0.025	D	0.523	0.383	0.380223377699	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
E/G	rs1310732379	-2.663	0.025	D	0.523	0.383	0.380223377699	gnomAD-4.0.0	1.59205E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8826E-05	0	0	0	0
E/K	None	None	0.892	D	0.684	0.411	0.411531665326	gnomAD-4.0.0	1.59205E-06	None	None	None	None	N	None	0	0	None	0	2.77562E-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
E/A	0.9406	likely_pathogenic	0.9611	pathogenic	-2.348	Highly Destabilizing	0.805	D	0.643	neutral	D	0.528772649	None	None	N
E/C	0.9943	likely_pathogenic	0.9957	pathogenic	-1.267	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/D	0.8557	likely_pathogenic	0.8549	pathogenic	-1.751	Destabilizing	0.892	D	0.636	neutral	N	0.497590569	None	None	N
E/F	0.9976	likely_pathogenic	0.9982	pathogenic	-2.065	Highly Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
E/G	0.9492	likely_pathogenic	0.9635	pathogenic	-2.705	Highly Destabilizing	0.025	N	0.523	neutral	D	0.530547076	None	None	N
E/H	0.9862	likely_pathogenic	0.9896	pathogenic	-1.791	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
E/I	0.9855	likely_pathogenic	0.992	pathogenic	-1.303	Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
E/K	0.943	likely_pathogenic	0.9664	pathogenic	-2.046	Highly Destabilizing	0.892	D	0.684	prob.neutral	D	0.523884351	None	None	N
E/L	0.9763	likely_pathogenic	0.9853	pathogenic	-1.303	Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	N
E/M	0.9738	likely_pathogenic	0.9841	pathogenic	-0.476	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
E/N	0.984	likely_pathogenic	0.9873	pathogenic	-2.096	Highly Destabilizing	0.975	D	0.793	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9999	pathogenic	-1.642	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
E/Q	0.6336	likely_pathogenic	0.7075	pathogenic	-1.852	Destabilizing	0.994	D	0.775	deleterious	N	0.513843773	None	None	N
E/R	0.9657	likely_pathogenic	0.977	pathogenic	-1.757	Destabilizing	0.987	D	0.81	deleterious	None	None	None	None	N
E/S	0.937	likely_pathogenic	0.9524	pathogenic	-2.846	Highly Destabilizing	0.916	D	0.677	prob.neutral	None	None	None	None	N
E/T	0.9707	likely_pathogenic	0.9797	pathogenic	-2.499	Highly Destabilizing	0.987	D	0.749	deleterious	None	None	None	None	N
E/V	0.9576	likely_pathogenic	0.9747	pathogenic	-1.642	Destabilizing	0.983	D	0.753	deleterious	D	0.522949752	None	None	N
E/W	0.9982	likely_pathogenic	0.9988	pathogenic	-2.045	Highly Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/Y	0.9948	likely_pathogenic	0.9963	pathogenic	-1.874	Destabilizing	0.996	D	0.798	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.