TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9511	28756;28757;28758	chr2:178709788;178709787;178709786	chr2:179574515;179574514;179574513
N2AB	9194	27805;27806;27807	chr2:178709788;178709787;178709786	chr2:179574515;179574514;179574513
N2A	8267	25024;25025;25026	chr2:178709788;178709787;178709786	chr2:179574515;179574514;179574513
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-81
• Domain position: 19
• Structural Position: 28
• Q(SASA): 0.1592
• 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	0.002	None	0.227	0.138	0.0986583533028	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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	0.927	likely_pathogenic	0.9008	pathogenic	-2.976	Highly Destabilizing	0.013	N	0.457	neutral	None	None	None	None	N
F/C	0.638	likely_pathogenic	0.5633	ambiguous	-2.403	Highly Destabilizing	0.975	D	0.691	prob.neutral	None	None	None	None	N
F/D	0.9974	likely_pathogenic	0.9972	pathogenic	-3.462	Highly Destabilizing	0.944	D	0.755	deleterious	None	None	None	None	N
F/E	0.9956	likely_pathogenic	0.9955	pathogenic	-3.235	Highly Destabilizing	0.828	D	0.743	deleterious	None	None	None	None	N
F/G	0.983	likely_pathogenic	0.9789	pathogenic	-3.456	Highly Destabilizing	0.704	D	0.691	prob.neutral	None	None	None	None	N
F/H	0.969	likely_pathogenic	0.9683	pathogenic	-2.07	Highly Destabilizing	0.995	D	0.697	prob.neutral	None	None	None	None	N
F/I	0.3349	likely_benign	0.2938	benign	-1.406	Destabilizing	0.27	N	0.493	neutral	None	None	None	None	N
F/K	0.9937	likely_pathogenic	0.9937	pathogenic	-2.597	Highly Destabilizing	0.828	D	0.721	prob.delet.	None	None	None	None	N
F/L	0.8082	likely_pathogenic	0.7687	pathogenic	-1.406	Destabilizing	0.002	N	0.227	neutral	None	None	None	None	N
F/M	0.7002	likely_pathogenic	0.6622	pathogenic	-1.275	Destabilizing	0.893	D	0.684	prob.neutral	None	None	None	None	N
F/N	0.989	likely_pathogenic	0.9891	pathogenic	-3.132	Highly Destabilizing	0.981	D	0.749	deleterious	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.9982	pathogenic	-1.943	Destabilizing	0.944	D	0.743	deleterious	None	None	None	None	N
F/Q	0.9891	likely_pathogenic	0.9886	pathogenic	-3.023	Highly Destabilizing	0.981	D	0.75	deleterious	None	None	None	None	N
F/R	0.9823	likely_pathogenic	0.9811	pathogenic	-2.143	Highly Destabilizing	0.944	D	0.744	deleterious	None	None	None	None	N
F/S	0.9599	likely_pathogenic	0.9494	pathogenic	-3.799	Highly Destabilizing	0.473	N	0.655	neutral	None	None	None	None	N
F/T	0.9345	likely_pathogenic	0.9203	pathogenic	-3.445	Highly Destabilizing	0.704	D	0.637	neutral	None	None	None	None	N
F/V	0.3366	likely_benign	0.2868	benign	-1.943	Destabilizing	0.01	N	0.388	neutral	None	None	None	None	N
F/W	0.8486	likely_pathogenic	0.8257	pathogenic	-0.505	Destabilizing	0.995	D	0.613	neutral	None	None	None	None	N
F/Y	0.5424	ambiguous	0.5225	ambiguous	-0.952	Destabilizing	0.784	D	0.593	neutral	None	None	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.