TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31402	94429;94430;94431	chr2:178547422;178547421;178547420	chr2:179412149;179412148;179412147
N2AB	29761	89506;89507;89508	chr2:178547422;178547421;178547420	chr2:179412149;179412148;179412147
N2A	28834	86725;86726;86727	chr2:178547422;178547421;178547420	chr2:179412149;179412148;179412147
N2B	22337	67234;67235;67236	chr2:178547422;178547421;178547420	chr2:179412149;179412148;179412147
Novex-1	22462	67609;67610;67611	chr2:178547422;178547421;178547420	chr2:179412149;179412148;179412147
Novex-2	22529	67810;67811;67812	chr2:178547422;178547421;178547420	chr2:179412149;179412148;179412147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-116
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0681
• 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
A/S	rs794729537	None	0.682	N	0.585	0.313	0.243398259712	gnomAD-4.0.0	6.90779E-07	None	None	None	None	N	None	0	2.29896E-05	None	0	0	None	0	0	0	0	0
A/T	rs794729537	None	0.682	N	0.608	0.277	0.267299060538	gnomAD-4.0.0	6.90779E-07	None	None	None	None	N	None	3.02425E-05	0	None	0	0	None	0	0	0	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
A/C	0.6587	likely_pathogenic	0.611	pathogenic	-1.384	Destabilizing	0.987	D	0.68	prob.neutral	None	None	None	None	N
A/D	0.9982	likely_pathogenic	0.9981	pathogenic	-2.569	Highly Destabilizing	0.979	D	0.725	deleterious	N	0.512728628	None	None	N
A/E	0.9936	likely_pathogenic	0.9934	pathogenic	-2.347	Highly Destabilizing	0.953	D	0.635	neutral	None	None	None	None	N
A/F	0.9525	likely_pathogenic	0.9652	pathogenic	-0.753	Destabilizing	0.909	D	0.711	prob.delet.	None	None	None	None	N
A/G	0.7155	likely_pathogenic	0.68	pathogenic	-1.779	Destabilizing	0.813	D	0.597	neutral	N	0.489090965	None	None	N
A/H	0.9963	likely_pathogenic	0.9965	pathogenic	-2.109	Highly Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
A/I	0.4658	ambiguous	0.502	ambiguous	-0.037	Destabilizing	0.037	N	0.461	neutral	None	None	None	None	N
A/K	0.997	likely_pathogenic	0.9976	pathogenic	-1.224	Destabilizing	0.953	D	0.642	neutral	None	None	None	None	N
A/L	0.5068	ambiguous	0.5863	pathogenic	-0.037	Destabilizing	0.37	N	0.549	neutral	None	None	None	None	N
A/M	0.7296	likely_pathogenic	0.7535	pathogenic	-0.49	Destabilizing	0.909	D	0.636	neutral	None	None	None	None	N
A/N	0.9893	likely_pathogenic	0.9864	pathogenic	-1.62	Destabilizing	0.984	D	0.71	prob.delet.	None	None	None	None	N
A/P	0.8469	likely_pathogenic	0.8005	pathogenic	-0.422	Destabilizing	0.979	D	0.678	prob.neutral	N	0.469834621	None	None	N
A/Q	0.9852	likely_pathogenic	0.9858	pathogenic	-1.379	Destabilizing	0.984	D	0.634	neutral	None	None	None	None	N
A/R	0.9881	likely_pathogenic	0.9905	pathogenic	-1.379	Destabilizing	0.953	D	0.632	neutral	None	None	None	None	N
A/S	0.4954	ambiguous	0.4454	ambiguous	-1.999	Destabilizing	0.682	D	0.585	neutral	N	0.493103436	None	None	N
A/T	0.519	ambiguous	0.4509	ambiguous	-1.655	Destabilizing	0.682	D	0.608	neutral	N	0.466098411	None	None	N
A/V	0.2587	likely_benign	0.2455	benign	-0.422	Destabilizing	0.007	N	0.362	neutral	N	0.508181663	None	None	N
A/W	0.9968	likely_pathogenic	0.9976	pathogenic	-1.492	Destabilizing	0.996	D	0.727	deleterious	None	None	None	None	N
A/Y	0.9911	likely_pathogenic	0.9934	pathogenic	-0.991	Destabilizing	0.953	D	0.709	prob.delet.	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.