TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28486	85681;85682;85683	chr2:178560676;178560675;178560674	chr2:179425403;179425402;179425401
N2AB	26845	80758;80759;80760	chr2:178560676;178560675;178560674	chr2:179425403;179425402;179425401
N2A	25918	77977;77978;77979	chr2:178560676;178560675;178560674	chr2:179425403;179425402;179425401
N2B	19421	58486;58487;58488	chr2:178560676;178560675;178560674	chr2:179425403;179425402;179425401
Novex-1	19546	58861;58862;58863	chr2:178560676;178560675;178560674	chr2:179425403;179425402;179425401
Novex-2	19613	59062;59063;59064	chr2:178560676;178560675;178560674	chr2:179425403;179425402;179425401
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-95
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.148
• 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
Y/C	None	None	1.0	D	0.883	0.873	0.903155408053	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
Y/A	0.983	likely_pathogenic	0.9837	pathogenic	-3.485	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
Y/C	0.6824	likely_pathogenic	0.6843	pathogenic	-1.503	Destabilizing	1.0	D	0.883	deleterious	D	0.664192256	None	None	N
Y/D	0.9733	likely_pathogenic	0.9782	pathogenic	-3.709	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.66439406	None	None	N
Y/E	0.9941	likely_pathogenic	0.9953	pathogenic	-3.496	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/F	0.1467	likely_benign	0.1416	benign	-1.61	Destabilizing	0.999	D	0.655	neutral	D	0.551179868	None	None	N
Y/G	0.9615	likely_pathogenic	0.964	pathogenic	-3.863	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/H	0.8799	likely_pathogenic	0.8809	pathogenic	-2.728	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.663788648	None	None	N
Y/I	0.8959	likely_pathogenic	0.8962	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/K	0.9905	likely_pathogenic	0.9925	pathogenic	-2.448	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.8201	likely_pathogenic	0.7989	pathogenic	-2.186	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
Y/M	0.9576	likely_pathogenic	0.9531	pathogenic	-1.715	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/N	0.9066	likely_pathogenic	0.9169	pathogenic	-3.225	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.664192256	None	None	N
Y/P	0.9948	likely_pathogenic	0.9956	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/Q	0.9862	likely_pathogenic	0.9876	pathogenic	-2.948	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.964	likely_pathogenic	0.9707	pathogenic	-2.302	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/S	0.9248	likely_pathogenic	0.927	pathogenic	-3.454	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.664192256	None	None	N
Y/T	0.9742	likely_pathogenic	0.9762	pathogenic	-3.129	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.8592	likely_pathogenic	0.8594	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
Y/W	0.71	likely_pathogenic	0.6975	pathogenic	-0.844	Destabilizing	1.0	D	0.783	deleterious	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.