TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15773	47542;47543;47544	chr2:178618034;178618033;178618032	chr2:179482761;179482760;179482759
N2AB	14132	42619;42620;42621	chr2:178618034;178618033;178618032	chr2:179482761;179482760;179482759
N2A	13205	39838;39839;39840	chr2:178618034;178618033;178618032	chr2:179482761;179482760;179482759
N2B	6708	20347;20348;20349	chr2:178618034;178618033;178618032	chr2:179482761;179482760;179482759
Novex-1	6833	20722;20723;20724	chr2:178618034;178618033;178618032	chr2:179482761;179482760;179482759
Novex-2	6900	20923;20924;20925	chr2:178618034;178618033;178618032	chr2:179482761;179482760;179482759
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: Fn3-2
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4406
• 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/Y	None	None	0.99	N	0.521	0.202	0.455081427078	gnomAD-4.0.0	1.59411E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86287E-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
F/A	0.6369	likely_pathogenic	0.5879	pathogenic	-0.838	Destabilizing	0.91	D	0.425	neutral	None	None	None	None	N
F/C	0.5934	likely_pathogenic	0.5338	ambiguous	-0.369	Destabilizing	0.999	D	0.576	neutral	N	0.505953652	None	None	N
F/D	0.7698	likely_pathogenic	0.7113	pathogenic	0.585	Stabilizing	0.986	D	0.637	neutral	None	None	None	None	N
F/E	0.8141	likely_pathogenic	0.7496	pathogenic	0.551	Stabilizing	0.986	D	0.631	neutral	None	None	None	None	N
F/G	0.8046	likely_pathogenic	0.7623	pathogenic	-1.004	Destabilizing	0.91	D	0.553	neutral	None	None	None	None	N
F/H	0.5612	ambiguous	0.5011	ambiguous	0.301	Stabilizing	0.999	D	0.499	neutral	None	None	None	None	N
F/I	0.5191	ambiguous	0.525	ambiguous	-0.432	Destabilizing	0.991	D	0.504	neutral	D	0.52865173	None	None	N
F/K	0.7998	likely_pathogenic	0.7362	pathogenic	-0.111	Destabilizing	0.986	D	0.635	neutral	None	None	None	None	N
F/L	0.921	likely_pathogenic	0.9102	pathogenic	-0.432	Destabilizing	0.939	D	0.447	neutral	D	0.529342159	None	None	N
F/M	0.6876	likely_pathogenic	0.649	pathogenic	-0.43	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	N
F/N	0.5923	likely_pathogenic	0.5299	ambiguous	-0.122	Destabilizing	0.986	D	0.647	neutral	None	None	None	None	N
F/P	0.9917	likely_pathogenic	0.9886	pathogenic	-0.548	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
F/Q	0.7524	likely_pathogenic	0.7013	pathogenic	-0.175	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
F/R	0.6818	likely_pathogenic	0.6342	pathogenic	0.327	Stabilizing	0.986	D	0.645	neutral	None	None	None	None	N
F/S	0.4568	ambiguous	0.4267	ambiguous	-0.722	Destabilizing	0.322	N	0.318	neutral	N	0.45013623	None	None	N
F/T	0.5864	likely_pathogenic	0.5386	ambiguous	-0.666	Destabilizing	0.91	D	0.493	neutral	None	None	None	None	N
F/V	0.486	ambiguous	0.4711	ambiguous	-0.548	Destabilizing	0.939	D	0.515	neutral	D	0.52883989	None	None	N
F/W	0.4826	ambiguous	0.4141	ambiguous	-0.348	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
F/Y	0.1701	likely_benign	0.1328	benign	-0.308	Destabilizing	0.99	D	0.521	neutral	N	0.477214922	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.