TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28328	85207;85208;85209	chr2:178561150;178561149;178561148	chr2:179425877;179425876;179425875
N2AB	26687	80284;80285;80286	chr2:178561150;178561149;178561148	chr2:179425877;179425876;179425875
N2A	25760	77503;77504;77505	chr2:178561150;178561149;178561148	chr2:179425877;179425876;179425875
N2B	19263	58012;58013;58014	chr2:178561150;178561149;178561148	chr2:179425877;179425876;179425875
Novex-1	19388	58387;58388;58389	chr2:178561150;178561149;178561148	chr2:179425877;179425876;179425875
Novex-2	19455	58588;58589;58590	chr2:178561150;178561149;178561148	chr2:179425877;179425876;179425875
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-94
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1067
• 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
F/L	rs1703507521	None	None	N	0.235	0.269	0.276482976112	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
F/A	0.5706	likely_pathogenic	0.4827	ambiguous	-3.365	Highly Destabilizing	0.228	N	0.612	neutral	None	None	None	None	N
F/C	0.3109	likely_benign	0.2637	benign	-1.923	Destabilizing	0.921	D	0.639	neutral	N	0.485214377	None	None	N
F/D	0.9617	likely_pathogenic	0.9365	pathogenic	-3.377	Highly Destabilizing	0.94	D	0.672	neutral	None	None	None	None	N
F/E	0.9351	likely_pathogenic	0.904	pathogenic	-3.233	Highly Destabilizing	0.593	D	0.677	prob.neutral	None	None	None	None	N
F/G	0.8837	likely_pathogenic	0.839	pathogenic	-3.728	Highly Destabilizing	0.593	D	0.639	neutral	None	None	None	None	N
F/H	0.6162	likely_pathogenic	0.5581	ambiguous	-1.981	Destabilizing	0.94	D	0.659	neutral	None	None	None	None	N
F/I	0.1714	likely_benign	0.1353	benign	-2.178	Highly Destabilizing	None	N	0.244	neutral	N	0.369061997	None	None	N
F/K	0.8225	likely_pathogenic	0.7757	pathogenic	-2.214	Highly Destabilizing	0.593	D	0.679	prob.neutral	None	None	None	None	N
F/L	0.6739	likely_pathogenic	0.6042	pathogenic	-2.178	Highly Destabilizing	None	N	0.235	neutral	N	0.417103873	None	None	N
F/M	0.3467	ambiguous	0.3105	benign	-1.767	Destabilizing	0.716	D	0.636	neutral	None	None	None	None	N
F/N	0.8161	likely_pathogenic	0.7439	pathogenic	-2.462	Highly Destabilizing	0.94	D	0.687	prob.neutral	None	None	None	None	N
F/P	0.9986	likely_pathogenic	0.9972	pathogenic	-2.583	Highly Destabilizing	0.94	D	0.686	prob.neutral	None	None	None	None	N
F/Q	0.7781	likely_pathogenic	0.7256	pathogenic	-2.585	Highly Destabilizing	0.94	D	0.677	prob.neutral	None	None	None	None	N
F/R	0.6899	likely_pathogenic	0.6315	pathogenic	-1.404	Destabilizing	0.836	D	0.683	prob.neutral	None	None	None	None	N
F/S	0.4966	ambiguous	0.398	ambiguous	-3.105	Highly Destabilizing	0.523	D	0.648	neutral	N	0.438556581	None	None	N
F/T	0.4507	ambiguous	0.3634	ambiguous	-2.874	Highly Destabilizing	0.418	N	0.653	neutral	None	None	None	None	N
F/V	0.2179	likely_benign	0.1722	benign	-2.583	Highly Destabilizing	0.021	N	0.507	neutral	N	0.445309195	None	None	N
F/W	0.4875	ambiguous	0.4711	ambiguous	-0.908	Destabilizing	0.983	D	0.663	neutral	None	None	None	None	N
F/Y	0.1937	likely_benign	0.1769	benign	-1.309	Destabilizing	0.523	D	0.6	neutral	N	0.468647414	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.