TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22519	67780;67781;67782	chr2:178579642;178579641;178579640	chr2:179444369;179444368;179444367
N2AB	20878	62857;62858;62859	chr2:178579642;178579641;178579640	chr2:179444369;179444368;179444367
N2A	19951	60076;60077;60078	chr2:178579642;178579641;178579640	chr2:179444369;179444368;179444367
N2B	13454	40585;40586;40587	chr2:178579642;178579641;178579640	chr2:179444369;179444368;179444367
Novex-1	13579	40960;40961;40962	chr2:178579642;178579641;178579640	chr2:179444369;179444368;179444367
Novex-2	13646	41161;41162;41163	chr2:178579642;178579641;178579640	chr2:179444369;179444368;179444367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-51
• Domain position: 69
• Structural Position: 104
• Q(SASA): 0.139
• 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/D	rs779007987	-3.311	1.0	D	0.887	0.917	0.921835126833	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/D	rs779007987	-3.311	1.0	D	0.887	0.917	0.921835126833	gnomAD-4.0.0	6.15957E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19748E-06	0	1.65717E-05

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	0.9634	likely_pathogenic	0.9645	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/C	0.6777	likely_pathogenic	0.6817	pathogenic	-1.249	Destabilizing	1.0	D	0.873	deleterious	D	0.663417144	None	None	N
Y/D	0.9755	likely_pathogenic	0.9757	pathogenic	-1.424	Destabilizing	1.0	D	0.887	deleterious	D	0.663417144	None	None	N
Y/E	0.9879	likely_pathogenic	0.9876	pathogenic	-1.251	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/F	0.1988	likely_benign	0.1869	benign	-0.602	Destabilizing	0.999	D	0.775	deleterious	D	0.616560963	None	None	N
Y/G	0.9404	likely_pathogenic	0.9452	pathogenic	-2.62	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/H	0.7897	likely_pathogenic	0.7725	pathogenic	-1.021	Destabilizing	1.0	D	0.846	deleterious	D	0.647397783	None	None	N
Y/I	0.8156	likely_pathogenic	0.7946	pathogenic	-1.015	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/K	0.9731	likely_pathogenic	0.9706	pathogenic	-1.464	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/L	0.8146	likely_pathogenic	0.8236	pathogenic	-1.015	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
Y/M	0.8762	likely_pathogenic	0.8711	pathogenic	-0.866	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/N	0.811	likely_pathogenic	0.8178	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.66321534	None	None	N
Y/P	0.9974	likely_pathogenic	0.9974	pathogenic	-1.424	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/Q	0.9708	likely_pathogenic	0.9708	pathogenic	-1.838	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/R	0.9511	likely_pathogenic	0.9509	pathogenic	-1.267	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/S	0.9273	likely_pathogenic	0.9307	pathogenic	-2.613	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.663417144	None	None	N
Y/T	0.9538	likely_pathogenic	0.9512	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/V	0.7562	likely_pathogenic	0.73	pathogenic	-1.424	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/W	0.7765	likely_pathogenic	0.7478	pathogenic	-0.006	Destabilizing	1.0	D	0.827	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.