TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27048	81367;81368;81369	chr2:178564990;178564989;178564988	chr2:179429717;179429716;179429715
N2AB	25407	76444;76445;76446	chr2:178564990;178564989;178564988	chr2:179429717;179429716;179429715
N2A	24480	73663;73664;73665	chr2:178564990;178564989;178564988	chr2:179429717;179429716;179429715
N2B	17983	54172;54173;54174	chr2:178564990;178564989;178564988	chr2:179429717;179429716;179429715
Novex-1	18108	54547;54548;54549	chr2:178564990;178564989;178564988	chr2:179429717;179429716;179429715
Novex-2	18175	54748;54749;54750	chr2:178564990;178564989;178564988	chr2:179429717;179429716;179429715
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: Fn3-84
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.0927
• 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	None	None	0.005	N	0.431	0.136	0.357519025918	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
F/S	None	None	None	N	0.5	0.14	0.261217442401	gnomAD-4.0.0	1.59558E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8638E-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	0.2463	likely_benign	0.2605	benign	-3.631	Highly Destabilizing	None	N	0.507	neutral	None	None	None	None	N
F/C	0.1312	likely_benign	0.1239	benign	-2.096	Highly Destabilizing	None	N	0.517	neutral	N	0.511880903	None	None	N
F/D	0.7874	likely_pathogenic	0.7848	pathogenic	-3.803	Highly Destabilizing	0.072	N	0.74	deleterious	None	None	None	None	N
F/E	0.796	likely_pathogenic	0.7898	pathogenic	-3.643	Highly Destabilizing	0.016	N	0.709	prob.delet.	None	None	None	None	N
F/G	0.6058	likely_pathogenic	0.5864	pathogenic	-3.997	Highly Destabilizing	0.016	N	0.719	prob.delet.	None	None	None	None	N
F/H	0.299	likely_benign	0.2902	benign	-2.279	Highly Destabilizing	None	N	0.641	neutral	None	None	None	None	N
F/I	0.2116	likely_benign	0.2045	benign	-2.408	Highly Destabilizing	0.012	N	0.537	neutral	N	0.461182724	None	None	N
F/K	0.7484	likely_pathogenic	0.7491	pathogenic	-2.491	Highly Destabilizing	None	N	0.611	neutral	None	None	None	None	N
F/L	0.6931	likely_pathogenic	0.6516	pathogenic	-2.408	Highly Destabilizing	0.005	N	0.431	neutral	N	0.498180887	None	None	N
F/M	0.3533	ambiguous	0.3348	benign	-1.933	Destabilizing	0.356	N	0.641	neutral	None	None	None	None	N
F/N	0.4673	ambiguous	0.453	ambiguous	-2.815	Highly Destabilizing	0.072	N	0.742	deleterious	None	None	None	None	N
F/P	0.9958	likely_pathogenic	0.9951	pathogenic	-2.829	Highly Destabilizing	0.136	N	0.762	deleterious	None	None	None	None	N
F/Q	0.5695	likely_pathogenic	0.5434	ambiguous	-2.911	Highly Destabilizing	0.072	N	0.758	deleterious	None	None	None	None	N
F/R	0.5441	ambiguous	0.5555	ambiguous	-1.678	Destabilizing	0.038	N	0.733	prob.delet.	None	None	None	None	N
F/S	0.1624	likely_benign	0.1737	benign	-3.419	Highly Destabilizing	None	N	0.5	neutral	N	0.446098629	None	None	N
F/T	0.2827	likely_benign	0.2893	benign	-3.174	Highly Destabilizing	0.016	N	0.702	prob.neutral	None	None	None	None	N
F/V	0.1843	likely_benign	0.1732	benign	-2.829	Highly Destabilizing	None	N	0.467	neutral	N	0.452043166	None	None	N
F/W	0.3995	ambiguous	0.3964	ambiguous	-1.099	Destabilizing	0.356	N	0.659	neutral	None	None	None	None	N
F/Y	0.1113	likely_benign	0.1023	benign	-1.566	Destabilizing	None	N	0.243	neutral	N	0.458950496	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.