TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3854	11785;11786;11787	chr2:178741673;178741672;178741671	chr2:179606400;179606399;179606398
N2AB	3537	10834;10835;10836	chr2:178741673;178741672;178741671	chr2:179606400;179606399;179606398
N2A	None	None	chr2:None	chr2:None
N2B	3491	10696;10697;10698	chr2:178741673;178741672;178741671	chr2:179606400;179606399;179606398
Novex-1	3616	11071;11072;11073	chr2:178741673;178741672;178741671	chr2:179606400;179606399;179606398
Novex-2	3683	11272;11273;11274	chr2:178741673;178741672;178741671	chr2:179606400;179606399;179606398
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-27
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1835
• 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	rs2082510082	None	0.026	N	0.287	0.213	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6491	likely_pathogenic	0.5717	pathogenic	-2.583	Highly Destabilizing	0.851	D	0.651	neutral	None	None	None	None	I
F/C	0.3202	likely_benign	0.2696	benign	-1.321	Destabilizing	0.999	D	0.713	prob.delet.	D	0.599769673	None	None	I
F/D	0.8572	likely_pathogenic	0.8138	pathogenic	-2.082	Highly Destabilizing	0.976	D	0.735	prob.delet.	None	None	None	None	I
F/E	0.8501	likely_pathogenic	0.8139	pathogenic	-1.941	Destabilizing	0.976	D	0.717	prob.delet.	None	None	None	None	I
F/G	0.8274	likely_pathogenic	0.7858	pathogenic	-2.968	Highly Destabilizing	0.919	D	0.705	prob.neutral	None	None	None	None	I
F/H	0.5035	ambiguous	0.4961	ambiguous	-1.252	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	I
F/I	0.2522	likely_benign	0.1939	benign	-1.372	Destabilizing	0.811	D	0.481	neutral	N	0.457407982	None	None	I
F/K	0.8212	likely_pathogenic	0.7611	pathogenic	-1.459	Destabilizing	0.976	D	0.717	prob.delet.	None	None	None	None	I
F/L	0.7702	likely_pathogenic	0.7223	pathogenic	-1.372	Destabilizing	0.026	N	0.287	neutral	N	0.421512091	None	None	I
F/M	0.5516	ambiguous	0.4829	ambiguous	-1.01	Destabilizing	0.976	D	0.581	neutral	None	None	None	None	I
F/N	0.5878	likely_pathogenic	0.5318	ambiguous	-1.655	Destabilizing	0.976	D	0.733	prob.delet.	None	None	None	None	I
F/P	0.9979	likely_pathogenic	0.9965	pathogenic	-1.778	Destabilizing	0.988	D	0.748	deleterious	None	None	None	None	I
F/Q	0.7573	likely_pathogenic	0.713	pathogenic	-1.73	Destabilizing	0.988	D	0.752	deleterious	None	None	None	None	I
F/R	0.675	likely_pathogenic	0.6104	pathogenic	-0.816	Destabilizing	0.988	D	0.749	deleterious	None	None	None	None	I
F/S	0.4582	ambiguous	0.3937	ambiguous	-2.411	Highly Destabilizing	0.251	N	0.496	neutral	N	0.460203579	None	None	I
F/T	0.6458	likely_pathogenic	0.5504	ambiguous	-2.175	Highly Destabilizing	0.851	D	0.674	neutral	None	None	None	None	I
F/V	0.2889	likely_benign	0.2259	benign	-1.778	Destabilizing	0.811	D	0.573	neutral	N	0.452609411	None	None	I
F/W	0.5184	ambiguous	0.5319	ambiguous	-0.356	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	I
F/Y	0.1022	likely_benign	0.1078	benign	-0.641	Destabilizing	0.946	D	0.514	neutral	N	0.412800151	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.