TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26374	79345;79346;79347	chr2:178567012;178567011;178567010	chr2:179431739;179431738;179431737
N2AB	24733	74422;74423;74424	chr2:178567012;178567011;178567010	chr2:179431739;179431738;179431737
N2A	23806	71641;71642;71643	chr2:178567012;178567011;178567010	chr2:179431739;179431738;179431737
N2B	17309	52150;52151;52152	chr2:178567012;178567011;178567010	chr2:179431739;179431738;179431737
Novex-1	17434	52525;52526;52527	chr2:178567012;178567011;178567010	chr2:179431739;179431738;179431737
Novex-2	17501	52726;52727;52728	chr2:178567012;178567011;178567010	chr2:179431739;179431738;179431737
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: Fn3-79
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.7347
• 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/G	rs878945480	None	0.999	N	0.639	0.525	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs878945480	None	0.999	N	0.639	0.525	None	gnomAD-4.0.0	2.03007E-06	None	None	None	None	I	None	3.49614E-05	0	None	0	0	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	0.3651	ambiguous	0.414	ambiguous	-0.714	Destabilizing	0.997	D	0.783	deleterious	N	0.493744179	None	None	I
E/C	0.9217	likely_pathogenic	0.9284	pathogenic	-0.359	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
E/D	0.2301	likely_benign	0.272	benign	-0.943	Destabilizing	0.997	D	0.674	prob.neutral	D	0.525053349	None	None	I
E/F	0.8526	likely_pathogenic	0.8678	pathogenic	0.118	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
E/G	0.599	likely_pathogenic	0.6696	pathogenic	-1.107	Destabilizing	0.999	D	0.639	neutral	N	0.517395069	None	None	I
E/H	0.7761	likely_pathogenic	0.8118	pathogenic	0.033	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
E/I	0.4246	ambiguous	0.4455	ambiguous	0.368	Stabilizing	0.999	D	0.782	deleterious	None	None	None	None	I
E/K	0.5875	likely_pathogenic	0.6601	pathogenic	-0.323	Destabilizing	0.997	D	0.758	deleterious	N	0.497516388	None	None	I
E/L	0.4868	ambiguous	0.5195	ambiguous	0.368	Stabilizing	0.999	D	0.729	deleterious	None	None	None	None	I
E/M	0.6157	likely_pathogenic	0.6473	pathogenic	0.704	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
E/N	0.5383	ambiguous	0.5993	pathogenic	-1.003	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	I
E/P	0.8366	likely_pathogenic	0.8629	pathogenic	0.028	Stabilizing	0.999	D	0.804	deleterious	None	None	None	None	I
E/Q	0.302	likely_benign	0.3155	benign	-0.833	Destabilizing	0.999	D	0.71	prob.delet.	N	0.504755435	None	None	I
E/R	0.7315	likely_pathogenic	0.7742	pathogenic	0.043	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	I
E/S	0.4829	ambiguous	0.524	ambiguous	-1.31	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	I
E/T	0.4195	ambiguous	0.4531	ambiguous	-0.969	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	I
E/V	0.2609	likely_benign	0.278	benign	0.028	Stabilizing	0.999	D	0.755	deleterious	N	0.501265824	None	None	I
E/W	0.9684	likely_pathogenic	0.9719	pathogenic	0.454	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/Y	0.8258	likely_pathogenic	0.8534	pathogenic	0.421	Stabilizing	1.0	D	0.805	deleterious	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.