TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29308	88147;88148;88149	chr2:178557340;178557339;178557338	chr2:179422067;179422066;179422065
N2AB	27667	83224;83225;83226	chr2:178557340;178557339;178557338	chr2:179422067;179422066;179422065
N2A	26740	80443;80444;80445	chr2:178557340;178557339;178557338	chr2:179422067;179422066;179422065
N2B	20243	60952;60953;60954	chr2:178557340;178557339;178557338	chr2:179422067;179422066;179422065
Novex-1	20368	61327;61328;61329	chr2:178557340;178557339;178557338	chr2:179422067;179422066;179422065
Novex-2	20435	61528;61529;61530	chr2:178557340;178557339;178557338	chr2:179422067;179422066;179422065
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: Fn3-101
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1003
• 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	0.874	0.908	0.866217808601	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.9936	likely_pathogenic	0.995	pathogenic	-2.911	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/C	0.8421	likely_pathogenic	0.858	pathogenic	-1.554	Destabilizing	1.0	D	0.874	deleterious	D	0.662952815	None	None	N
Y/D	0.9955	likely_pathogenic	0.9957	pathogenic	-3.352	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.678972176	None	None	N
Y/E	0.9983	likely_pathogenic	0.9985	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/F	0.3346	likely_benign	0.3453	ambiguous	-0.955	Destabilizing	0.999	D	0.735	prob.delet.	D	0.626311878	None	None	N
Y/G	0.9852	likely_pathogenic	0.9877	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/H	0.9332	likely_pathogenic	0.9369	pathogenic	-1.997	Destabilizing	1.0	D	0.831	deleterious	D	0.678972176	None	None	N
Y/I	0.9807	likely_pathogenic	0.9863	pathogenic	-1.491	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/K	0.9964	likely_pathogenic	0.9972	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/L	0.9311	likely_pathogenic	0.9429	pathogenic	-1.491	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
Y/M	0.9817	likely_pathogenic	0.9845	pathogenic	-1.208	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/N	0.9636	likely_pathogenic	0.9635	pathogenic	-2.925	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.678770371	None	None	N
Y/P	0.9977	likely_pathogenic	0.998	pathogenic	-1.98	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/Q	0.9953	likely_pathogenic	0.9959	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/R	0.986	likely_pathogenic	0.9877	pathogenic	-1.939	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/S	0.9681	likely_pathogenic	0.9706	pathogenic	-3.254	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.678972176	None	None	N
Y/T	0.9898	likely_pathogenic	0.9914	pathogenic	-2.911	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/V	0.9546	likely_pathogenic	0.9663	pathogenic	-1.98	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.7526	likely_pathogenic	0.778	pathogenic	-0.261	Destabilizing	1.0	D	0.814	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.