TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27165	81718;81719;81720	chr2:178564639;178564638;178564637	chr2:179429366;179429365;179429364
N2AB	25524	76795;76796;76797	chr2:178564639;178564638;178564637	chr2:179429366;179429365;179429364
N2A	24597	74014;74015;74016	chr2:178564639;178564638;178564637	chr2:179429366;179429365;179429364
N2B	18100	54523;54524;54525	chr2:178564639;178564638;178564637	chr2:179429366;179429365;179429364
Novex-1	18225	54898;54899;54900	chr2:178564639;178564638;178564637	chr2:179429366;179429365;179429364
Novex-2	18292	55099;55100;55101	chr2:178564639;178564638;178564637	chr2:179429366;179429365;179429364
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: Fn3-85
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.1859
• 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/S	rs1413349026	None	0.006	N	0.343	0.061	0.430239905395	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/S	rs1413349026	None	0.006	N	0.343	0.061	0.430239905395	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47046E-05	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	0.4	ambiguous	0.3699	ambiguous	-2.461	Highly Destabilizing	None	N	0.287	neutral	None	None	None	None	N
F/C	0.144	likely_benign	0.1306	benign	-1.419	Destabilizing	0.371	N	0.487	neutral	N	0.516206501	None	None	N
F/D	0.8076	likely_pathogenic	0.7685	pathogenic	-2.332	Highly Destabilizing	0.068	N	0.535	neutral	None	None	None	None	N
F/E	0.8029	likely_pathogenic	0.799	pathogenic	-2.161	Highly Destabilizing	0.068	N	0.451	neutral	None	None	None	None	N
F/G	0.7233	likely_pathogenic	0.6655	pathogenic	-2.868	Highly Destabilizing	0.015	N	0.346	neutral	None	None	None	None	N
F/H	0.3685	ambiguous	0.355	ambiguous	-1.196	Destabilizing	0.112	N	0.392	neutral	None	None	None	None	N
F/I	0.1542	likely_benign	0.1478	benign	-1.164	Destabilizing	0.006	N	0.321	neutral	N	0.44569041	None	None	N
F/K	0.7503	likely_pathogenic	0.767	pathogenic	-1.731	Destabilizing	0.035	N	0.449	neutral	None	None	None	None	N
F/L	0.7412	likely_pathogenic	0.7056	pathogenic	-1.164	Destabilizing	0.002	N	0.29	neutral	N	0.477474754	None	None	N
F/M	0.4156	ambiguous	0.3938	ambiguous	-0.809	Destabilizing	0.204	N	0.389	neutral	None	None	None	None	N
F/N	0.5778	likely_pathogenic	0.5342	ambiguous	-2.088	Highly Destabilizing	0.068	N	0.535	neutral	None	None	None	None	N
F/P	0.9699	likely_pathogenic	0.9593	pathogenic	-1.601	Destabilizing	0.068	N	0.561	neutral	None	None	None	None	N
F/Q	0.6204	likely_pathogenic	0.6286	pathogenic	-2.079	Highly Destabilizing	0.068	N	0.594	neutral	None	None	None	None	N
F/R	0.6039	likely_pathogenic	0.6108	pathogenic	-1.194	Destabilizing	0.035	N	0.571	neutral	None	None	None	None	N
F/S	0.3165	likely_benign	0.2789	benign	-2.779	Highly Destabilizing	0.006	N	0.343	neutral	N	0.515339709	None	None	N
F/T	0.3219	likely_benign	0.3026	benign	-2.5	Highly Destabilizing	None	N	0.257	neutral	None	None	None	None	N
F/V	0.1335	likely_benign	0.1333	benign	-1.601	Destabilizing	None	N	0.19	neutral	N	0.390759847	None	None	N
F/W	0.3979	ambiguous	0.3419	ambiguous	-0.283	Destabilizing	0.204	N	0.431	neutral	None	None	None	None	N
F/Y	0.0907	likely_benign	0.0843	benign	-0.596	Destabilizing	None	N	0.108	neutral	N	0.41890924	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.