TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33204	99835;99836;99837	chr2:178537597;178537596;178537595	chr2:179402324;179402323;179402322
N2AB	31563	94912;94913;94914	chr2:178537597;178537596;178537595	chr2:179402324;179402323;179402322
N2A	30636	92131;92132;92133	chr2:178537597;178537596;178537595	chr2:179402324;179402323;179402322
N2B	24139	72640;72641;72642	chr2:178537597;178537596;178537595	chr2:179402324;179402323;179402322
Novex-1	24264	73015;73016;73017	chr2:178537597;178537596;178537595	chr2:179402324;179402323;179402322
Novex-2	24331	73216;73217;73218	chr2:178537597;178537596;178537595	chr2:179402324;179402323;179402322
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: Ig-157
• Domain position: 2
• Structural Position: 9
• Q(SASA): 0.7069
• 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	0.941	N	0.523	0.219	0.417843521124	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
E/K	rs1490008675	0.445	0.996	N	0.644	0.457	0.388010793773	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs1490008675	0.445	0.996	N	0.644	0.457	0.388010793773	gnomAD-4.0.0	2.05285E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31879E-05	1.65678E-05
E/V	None	None	0.996	N	0.698	0.545	0.53754225682	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85891E-06	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	0.314	likely_benign	0.3331	benign	-0.041	Destabilizing	0.992	D	0.636	neutral	N	0.508254313	None	None	N
E/C	0.9507	likely_pathogenic	0.9594	pathogenic	-0.284	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/D	0.1827	likely_benign	0.1882	benign	-0.328	Destabilizing	0.941	D	0.523	neutral	N	0.440413168	None	None	N
E/F	0.9424	likely_pathogenic	0.9471	pathogenic	-0.042	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/G	0.1921	likely_benign	0.1993	benign	-0.161	Destabilizing	0.999	D	0.645	neutral	N	0.508947747	None	None	N
E/H	0.7683	likely_pathogenic	0.7464	pathogenic	0.615	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/I	0.749	likely_pathogenic	0.7796	pathogenic	0.22	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/K	0.3049	likely_benign	0.2931	benign	0.374	Stabilizing	0.996	D	0.644	neutral	N	0.470389358	None	None	N
E/L	0.744	likely_pathogenic	0.7718	pathogenic	0.22	Stabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
E/M	0.7603	likely_pathogenic	0.7855	pathogenic	-0.06	Destabilizing	0.997	D	0.715	prob.delet.	None	None	None	None	N
E/N	0.4041	ambiguous	0.388	ambiguous	0.101	Stabilizing	0.996	D	0.667	neutral	None	None	None	None	N
E/P	0.6258	likely_pathogenic	0.6019	pathogenic	0.151	Stabilizing	0.987	D	0.655	neutral	None	None	None	None	N
E/Q	0.2566	likely_benign	0.2474	benign	0.109	Stabilizing	0.998	D	0.575	neutral	N	0.477931406	None	None	N
E/R	0.4885	ambiguous	0.469	ambiguous	0.662	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/S	0.3666	ambiguous	0.3595	ambiguous	-0.044	Destabilizing	0.994	D	0.622	neutral	None	None	None	None	N
E/T	0.4512	ambiguous	0.462	ambiguous	0.062	Stabilizing	0.999	D	0.646	neutral	None	None	None	None	N
E/V	0.5013	ambiguous	0.5534	ambiguous	0.151	Stabilizing	0.996	D	0.698	prob.neutral	N	0.507907597	None	None	N
E/W	0.9673	likely_pathogenic	0.9655	pathogenic	0.019	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/Y	0.8574	likely_pathogenic	0.8644	pathogenic	0.186	Stabilizing	1.0	D	0.711	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.