TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26770	80533;80534;80535	chr2:178565824;178565823;178565822	chr2:179430551;179430550;179430549
N2AB	25129	75610;75611;75612	chr2:178565824;178565823;178565822	chr2:179430551;179430550;179430549
N2A	24202	72829;72830;72831	chr2:178565824;178565823;178565822	chr2:179430551;179430550;179430549
N2B	17705	53338;53339;53340	chr2:178565824;178565823;178565822	chr2:179430551;179430550;179430549
Novex-1	17830	53713;53714;53715	chr2:178565824;178565823;178565822	chr2:179430551;179430550;179430549
Novex-2	17897	53914;53915;53916	chr2:178565824;178565823;178565822	chr2:179430551;179430550;179430549
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: Fn3-82
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.2913
• 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	0.004	N	0.434	0.118	0.21279746466	gnomAD-4.0.0	5.47416E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19646E-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	0.3767	ambiguous	0.362	ambiguous	-0.732	Destabilizing	0.916	D	0.521	neutral	N	0.469376867	None	None	N
E/C	0.9342	likely_pathogenic	0.9373	pathogenic	-0.419	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/D	0.3507	ambiguous	0.366	ambiguous	-0.963	Destabilizing	0.004	N	0.434	neutral	N	0.469630357	None	None	N
E/F	0.9281	likely_pathogenic	0.9243	pathogenic	0.151	Stabilizing	0.995	D	0.722	deleterious	None	None	None	None	N
E/G	0.603	likely_pathogenic	0.5637	ambiguous	-1.138	Destabilizing	0.987	D	0.604	neutral	N	0.505727189	None	None	N
E/H	0.8358	likely_pathogenic	0.8408	pathogenic	-0.016	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
E/I	0.6277	likely_pathogenic	0.6336	pathogenic	0.389	Stabilizing	0.957	D	0.642	neutral	None	None	None	None	N
E/K	0.5798	likely_pathogenic	0.5561	ambiguous	-0.489	Destabilizing	0.976	D	0.527	neutral	N	0.477721433	None	None	N
E/L	0.7184	likely_pathogenic	0.708	pathogenic	0.389	Stabilizing	0.863	D	0.677	prob.neutral	None	None	None	None	N
E/M	0.6817	likely_pathogenic	0.6722	pathogenic	0.752	Stabilizing	0.984	D	0.658	prob.neutral	None	None	None	None	N
E/N	0.6688	likely_pathogenic	0.6556	pathogenic	-1.124	Destabilizing	0.954	D	0.501	neutral	None	None	None	None	N
E/P	0.9325	likely_pathogenic	0.9234	pathogenic	0.036	Stabilizing	0.976	D	0.521	neutral	None	None	None	None	N
E/Q	0.3445	ambiguous	0.3379	benign	-0.944	Destabilizing	0.99	D	0.537	neutral	N	0.478886748	None	None	N
E/R	0.7614	likely_pathogenic	0.745	pathogenic	-0.126	Destabilizing	0.995	D	0.499	neutral	None	None	None	None	N
E/S	0.4936	ambiguous	0.4925	ambiguous	-1.467	Destabilizing	0.936	D	0.504	neutral	None	None	None	None	N
E/T	0.4541	ambiguous	0.4517	ambiguous	-1.118	Destabilizing	0.953	D	0.534	neutral	None	None	None	None	N
E/V	0.3988	ambiguous	0.4009	ambiguous	0.036	Stabilizing	0.173	N	0.583	neutral	N	0.47378464	None	None	N
E/W	0.9842	likely_pathogenic	0.9849	pathogenic	0.476	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
E/Y	0.9097	likely_pathogenic	0.91	pathogenic	0.44	Stabilizing	0.999	D	0.692	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.