TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6569	19930;19931;19932	chr2:178728119;178728118;178728117	chr2:179592846;179592845;179592844
N2AB	6252	18979;18980;18981	chr2:178728119;178728118;178728117	chr2:179592846;179592845;179592844
N2A	5325	16198;16199;16200	chr2:178728119;178728118;178728117	chr2:179592846;179592845;179592844
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-49
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3007
• 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
T/A	rs1428304417	-0.465	0.472	N	0.384	0.247	0.241664281697	gnomAD-2.1.1	4.61E-06	None	None	None	None	N	None	0	0	None	0	0	None	4.44E-05	None	0	0	0
T/A	rs1428304417	-0.465	0.472	N	0.384	0.247	0.241664281697	gnomAD-4.0.0	1.70176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.61891E-05	0
T/I	None	None	0.792	N	0.393	0.212	0.431490205687	gnomAD-4.0.0	1.70386E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.55493E-04	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
T/A	0.1099	likely_benign	0.1166	benign	-0.871	Destabilizing	0.472	N	0.384	neutral	N	0.492974165	None	None	N
T/C	0.6122	likely_pathogenic	0.5952	pathogenic	-0.636	Destabilizing	0.996	D	0.422	neutral	None	None	None	None	N
T/D	0.4803	ambiguous	0.4928	ambiguous	-0.559	Destabilizing	0.59	D	0.393	neutral	None	None	None	None	N
T/E	0.343	ambiguous	0.3613	ambiguous	-0.537	Destabilizing	0.59	D	0.4	neutral	None	None	None	None	N
T/F	0.2344	likely_benign	0.2317	benign	-0.84	Destabilizing	0.91	D	0.505	neutral	None	None	None	None	N
T/G	0.4251	ambiguous	0.4631	ambiguous	-1.155	Destabilizing	0.59	D	0.486	neutral	None	None	None	None	N
T/H	0.2567	likely_benign	0.2501	benign	-1.414	Destabilizing	0.953	D	0.478	neutral	None	None	None	None	N
T/I	0.1788	likely_benign	0.1922	benign	-0.198	Destabilizing	0.792	D	0.393	neutral	N	0.507182452	None	None	N
T/K	0.2404	likely_benign	0.2599	benign	-0.834	Destabilizing	0.59	D	0.41	neutral	None	None	None	None	N
T/L	0.1091	likely_benign	0.1166	benign	-0.198	Destabilizing	0.009	N	0.29	neutral	None	None	None	None	N
T/M	0.0883	likely_benign	0.0948	benign	0.098	Stabilizing	0.91	D	0.42	neutral	None	None	None	None	N
T/N	0.1535	likely_benign	0.1514	benign	-0.861	Destabilizing	0.015	N	0.278	neutral	N	0.49744439	None	None	N
T/P	0.4954	ambiguous	0.5475	ambiguous	-0.39	Destabilizing	0.979	D	0.429	neutral	D	0.54126345	None	None	N
T/Q	0.2456	likely_benign	0.2615	benign	-1.027	Destabilizing	0.206	N	0.329	neutral	None	None	None	None	N
T/R	0.1679	likely_benign	0.182	benign	-0.603	Destabilizing	0.02	N	0.298	neutral	None	None	None	None	N
T/S	0.151	likely_benign	0.1505	benign	-1.133	Destabilizing	0.521	D	0.398	neutral	D	0.523285268	None	None	N
T/V	0.1579	likely_benign	0.171	benign	-0.39	Destabilizing	0.59	D	0.371	neutral	None	None	None	None	N
T/W	0.5655	likely_pathogenic	0.5941	pathogenic	-0.771	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
T/Y	0.2705	likely_benign	0.2745	benign	-0.536	Destabilizing	0.984	D	0.499	neutral	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.