TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19269	58030;58031;58032	chr2:178595549;178595548;178595547	chr2:179460276;179460275;179460274
N2AB	17628	53107;53108;53109	chr2:178595549;178595548;178595547	chr2:179460276;179460275;179460274
N2A	16701	50326;50327;50328	chr2:178595549;178595548;178595547	chr2:179460276;179460275;179460274
N2B	10204	30835;30836;30837	chr2:178595549;178595548;178595547	chr2:179460276;179460275;179460274
Novex-1	10329	31210;31211;31212	chr2:178595549;178595548;178595547	chr2:179460276;179460275;179460274
Novex-2	10396	31411;31412;31413	chr2:178595549;178595548;178595547	chr2:179460276;179460275;179460274
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: Fn3-27
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.4576
• 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
F/L	rs1214774748	None	0.698	N	0.656	0.348	0.304435445954	gnomAD-4.0.0	3.43113E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.15184E-06	0	0
F/S	None	None	0.942	N	0.756	0.303	0.691616392624	gnomAD-4.0.0	3.4326E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.15362E-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	0.8181	likely_pathogenic	0.8505	pathogenic	-2.426	Highly Destabilizing	0.86	D	0.697	prob.neutral	None	None	None	None	I
F/C	0.575	likely_pathogenic	0.6591	pathogenic	-1.006	Destabilizing	0.997	D	0.761	deleterious	N	0.485937413	None	None	I
F/D	0.9727	likely_pathogenic	0.9797	pathogenic	-1.6	Destabilizing	0.993	D	0.789	deleterious	None	None	None	None	I
F/E	0.979	likely_pathogenic	0.9819	pathogenic	-1.517	Destabilizing	0.978	D	0.783	deleterious	None	None	None	None	I
F/G	0.9314	likely_pathogenic	0.9487	pathogenic	-2.757	Highly Destabilizing	0.978	D	0.76	deleterious	None	None	None	None	I
F/H	0.8128	likely_pathogenic	0.8422	pathogenic	-0.973	Destabilizing	0.956	D	0.779	deleterious	None	None	None	None	I
F/I	0.796	likely_pathogenic	0.828	pathogenic	-1.412	Destabilizing	0.942	D	0.695	prob.neutral	N	0.484416476	None	None	I
F/K	0.9811	likely_pathogenic	0.9823	pathogenic	-1.397	Destabilizing	0.956	D	0.787	deleterious	None	None	None	None	I
F/L	0.9615	likely_pathogenic	0.9653	pathogenic	-1.412	Destabilizing	0.698	D	0.656	neutral	N	0.471792723	None	None	I
F/M	0.8342	likely_pathogenic	0.8527	pathogenic	-0.903	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
F/N	0.9187	likely_pathogenic	0.9279	pathogenic	-1.453	Destabilizing	0.978	D	0.793	deleterious	None	None	None	None	I
F/P	0.9194	likely_pathogenic	0.9349	pathogenic	-1.747	Destabilizing	0.993	D	0.789	deleterious	None	None	None	None	I
F/Q	0.9609	likely_pathogenic	0.9646	pathogenic	-1.586	Destabilizing	0.978	D	0.791	deleterious	None	None	None	None	I
F/R	0.9554	likely_pathogenic	0.96	pathogenic	-0.634	Destabilizing	0.978	D	0.793	deleterious	None	None	None	None	I
F/S	0.7657	likely_pathogenic	0.8185	pathogenic	-2.154	Highly Destabilizing	0.942	D	0.756	deleterious	N	0.503546635	None	None	I
F/T	0.8837	likely_pathogenic	0.8997	pathogenic	-1.984	Destabilizing	0.978	D	0.758	deleterious	None	None	None	None	I
F/V	0.6847	likely_pathogenic	0.723	pathogenic	-1.747	Destabilizing	0.822	D	0.721	prob.delet.	N	0.472806681	None	None	I
F/W	0.537	ambiguous	0.6475	pathogenic	-0.584	Destabilizing	0.994	D	0.721	prob.delet.	None	None	None	None	I
F/Y	0.2276	likely_benign	0.2588	benign	-0.817	Destabilizing	0.014	N	0.466	neutral	N	0.447807995	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.