TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8246	24961;24962;24963	chr2:178718370;178718369;178718368	chr2:179583097;179583096;179583095
N2AB	7929	24010;24011;24012	chr2:178718370;178718369;178718368	chr2:179583097;179583096;179583095
N2A	7002	21229;21230;21231	chr2:178718370;178718369;178718368	chr2:179583097;179583096;179583095
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-67
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.376
• Predicted PPI site: I

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	rs578260569	-0.008	0.27	N	0.283	0.186	None	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.61558E-04	None	0	0	0
E/K	rs578260569	-0.008	0.27	N	0.283	0.186	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
E/K	rs578260569	-0.008	0.27	N	0.283	0.186	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs578260569	-0.008	0.27	N	0.283	0.186	None	gnomAD-4.0.0	1.67307E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47649E-07	2.85488E-04	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	0.1688	likely_benign	0.1628	benign	-0.861	Destabilizing	0.002	N	0.187	neutral	N	0.512606914	None	None	I
E/C	0.8441	likely_pathogenic	0.8239	pathogenic	-0.337	Destabilizing	0.985	D	0.526	neutral	None	None	None	None	I
E/D	0.2563	likely_benign	0.2233	benign	-1.062	Destabilizing	0.425	N	0.266	neutral	D	0.530539314	None	None	I
E/F	0.7551	likely_pathogenic	0.7235	pathogenic	-0.844	Destabilizing	0.007	N	0.452	neutral	None	None	None	None	I
E/G	0.1771	likely_benign	0.1729	benign	-1.161	Destabilizing	0.27	N	0.476	neutral	N	0.498863195	None	None	I
E/H	0.3926	ambiguous	0.3633	ambiguous	-1.099	Destabilizing	0.981	D	0.467	neutral	None	None	None	None	I
E/I	0.417	ambiguous	0.4066	ambiguous	-0.062	Destabilizing	0.704	D	0.561	neutral	None	None	None	None	I
E/K	0.1026	likely_benign	0.1085	benign	-0.279	Destabilizing	0.27	N	0.283	neutral	N	0.503139282	None	None	I
E/L	0.4533	ambiguous	0.4374	ambiguous	-0.062	Destabilizing	0.329	N	0.503	neutral	None	None	None	None	I
E/M	0.4615	ambiguous	0.4451	ambiguous	0.412	Stabilizing	0.981	D	0.51	neutral	None	None	None	None	I
E/N	0.3157	likely_benign	0.2884	benign	-0.598	Destabilizing	0.704	D	0.297	neutral	None	None	None	None	I
E/P	0.9777	likely_pathogenic	0.9711	pathogenic	-0.308	Destabilizing	0.944	D	0.482	neutral	None	None	None	None	I
E/Q	0.0954	likely_benign	0.0962	benign	-0.555	Destabilizing	0.642	D	0.385	neutral	D	0.531635392	None	None	I
E/R	0.176	likely_benign	0.1796	benign	-0.238	Destabilizing	0.007	N	0.203	neutral	None	None	None	None	I
E/S	0.1774	likely_benign	0.1691	benign	-0.926	Destabilizing	0.013	N	0.108	neutral	None	None	None	None	I
E/T	0.1911	likely_benign	0.1784	benign	-0.666	Destabilizing	0.329	N	0.387	neutral	None	None	None	None	I
E/V	0.2605	likely_benign	0.2528	benign	-0.308	Destabilizing	0.473	N	0.508	neutral	N	0.514743142	None	None	I
E/W	0.8856	likely_pathogenic	0.8527	pathogenic	-0.712	Destabilizing	0.995	D	0.539	neutral	None	None	None	None	I
E/Y	0.6444	likely_pathogenic	0.5987	pathogenic	-0.578	Destabilizing	0.807	D	0.533	neutral	None	None	None	None	I

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.