TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17133	51622;51623;51624	chr2:178610129;178610128;178610127	chr2:179474856;179474855;179474854
N2AB	15492	46699;46700;46701	chr2:178610129;178610128;178610127	chr2:179474856;179474855;179474854
N2A	14565	43918;43919;43920	chr2:178610129;178610128;178610127	chr2:179474856;179474855;179474854
N2B	8068	24427;24428;24429	chr2:178610129;178610128;178610127	chr2:179474856;179474855;179474854
Novex-1	8193	24802;24803;24804	chr2:178610129;178610128;178610127	chr2:179474856;179474855;179474854
Novex-2	8260	25003;25004;25005	chr2:178610129;178610128;178610127	chr2:179474856;179474855;179474854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-12
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.0772
• 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
I/T	rs373628708	None	0.651	N	0.687	0.183	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs373628708	None	0.651	N	0.687	0.183	None	gnomAD-4.0.0	2.48012E-06	None	None	None	None	N	None	1.33579E-05	0	None	0	0	None	0	0	2.54383E-06	0	0
I/V	None	None	0.01	N	0.153	0.065	0.362160248664	gnomAD-4.0.0	1.59313E-06	None	None	None	None	N	None	0	0	None	0	2.78443E-05	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
I/A	0.1099	likely_benign	0.1493	benign	-1.811	Destabilizing	0.505	D	0.602	neutral	None	None	None	None	N
I/C	0.4756	ambiguous	0.5131	ambiguous	-1.047	Destabilizing	0.995	D	0.568	neutral	None	None	None	None	N
I/D	0.5889	likely_pathogenic	0.6897	pathogenic	-1.193	Destabilizing	0.982	D	0.791	deleterious	None	None	None	None	N
I/E	0.3936	ambiguous	0.4758	ambiguous	-1.152	Destabilizing	0.982	D	0.769	deleterious	None	None	None	None	N
I/F	0.1861	likely_benign	0.2555	benign	-1.131	Destabilizing	0.868	D	0.71	prob.delet.	N	0.469530062	None	None	N
I/G	0.4149	ambiguous	0.5235	ambiguous	-2.178	Highly Destabilizing	0.982	D	0.763	deleterious	None	None	None	None	N
I/H	0.3887	ambiguous	0.4966	ambiguous	-1.372	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
I/K	0.2543	likely_benign	0.3272	benign	-1.302	Destabilizing	0.946	D	0.764	deleterious	None	None	None	None	N
I/L	0.0885	likely_benign	0.1028	benign	-0.852	Destabilizing	0.001	N	0.196	neutral	N	0.335330638	None	None	N
I/M	0.0771	likely_benign	0.0927	benign	-0.676	Destabilizing	0.868	D	0.66	prob.neutral	N	0.499332894	None	None	N
I/N	0.2003	likely_benign	0.2643	benign	-1.133	Destabilizing	0.976	D	0.783	deleterious	N	0.461892013	None	None	N
I/P	0.8158	likely_pathogenic	0.8744	pathogenic	-1.142	Destabilizing	0.982	D	0.781	deleterious	None	None	None	None	N
I/Q	0.2674	likely_benign	0.3234	benign	-1.258	Destabilizing	0.982	D	0.764	deleterious	None	None	None	None	N
I/R	0.1949	likely_benign	0.2528	benign	-0.75	Destabilizing	0.946	D	0.784	deleterious	None	None	None	None	N
I/S	0.1471	likely_benign	0.1883	benign	-1.788	Destabilizing	0.93	D	0.675	prob.neutral	N	0.333740623	None	None	N
I/T	0.062	likely_benign	0.0761	benign	-1.629	Destabilizing	0.651	D	0.687	prob.delet.	N	0.401054198	None	None	N
I/V	0.0621	likely_benign	0.0648	benign	-1.142	Destabilizing	0.01	N	0.153	neutral	N	0.384431307	None	None	N
I/W	0.7453	likely_pathogenic	0.8207	pathogenic	-1.24	Destabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
I/Y	0.5307	ambiguous	0.617	pathogenic	-1.024	Destabilizing	0.946	D	0.708	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.