TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14517	43774;43775;43776	chr2:178632345;178632344;178632343	chr2:179497072;179497071;179497070
N2AB	12876	38851;38852;38853	chr2:178632345;178632344;178632343	chr2:179497072;179497071;179497070
N2A	11949	36070;36071;36072	chr2:178632345;178632344;178632343	chr2:179497072;179497071;179497070
N2B	5452	16579;16580;16581	chr2:178632345;178632344;178632343	chr2:179497072;179497071;179497070
Novex-1	5577	16954;16955;16956	chr2:178632345;178632344;178632343	chr2:179497072;179497071;179497070
Novex-2	5644	17155;17156;17157	chr2:178632345;178632344;178632343	chr2:179497072;179497071;179497070
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-96
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4906
• 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	rs2154220669	None	0.454	N	0.462	0.256	0.449088463789	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs2154220669	None	0.454	N	0.462	0.256	0.449088463789	gnomAD-4.0.0	6.5722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47137E-05	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	0.1098	likely_benign	0.106	benign	-0.92	Destabilizing	0.454	N	0.462	neutral	N	0.505543134	None	None	N
T/C	0.5128	ambiguous	0.5119	ambiguous	-0.569	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
T/D	0.4464	ambiguous	0.4219	ambiguous	0.05	Stabilizing	0.842	D	0.528	neutral	None	None	None	None	N
T/E	0.2929	likely_benign	0.2675	benign	0.118	Stabilizing	0.842	D	0.519	neutral	None	None	None	None	N
T/F	0.2805	likely_benign	0.2784	benign	-0.887	Destabilizing	0.949	D	0.643	neutral	None	None	None	None	N
T/G	0.4065	ambiguous	0.3956	ambiguous	-1.233	Destabilizing	0.842	D	0.547	neutral	None	None	None	None	N
T/H	0.2468	likely_benign	0.2316	benign	-1.429	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
T/I	0.1842	likely_benign	0.1748	benign	-0.157	Destabilizing	0.012	N	0.389	neutral	N	0.463049243	None	None	N
T/K	0.1871	likely_benign	0.1651	benign	-0.418	Destabilizing	0.842	D	0.525	neutral	None	None	None	None	N
T/L	0.1362	likely_benign	0.1292	benign	-0.157	Destabilizing	0.525	D	0.483	neutral	None	None	None	None	N
T/M	0.104	likely_benign	0.103	benign	-0.07	Destabilizing	0.949	D	0.618	neutral	None	None	None	None	N
T/N	0.1668	likely_benign	0.1554	benign	-0.575	Destabilizing	0.801	D	0.506	neutral	N	0.503970995	None	None	N
T/P	0.3498	ambiguous	0.3243	benign	-0.378	Destabilizing	0.966	D	0.587	neutral	N	0.507803446	None	None	N
T/Q	0.2378	likely_benign	0.2181	benign	-0.589	Destabilizing	0.974	D	0.613	neutral	None	None	None	None	N
T/R	0.1344	likely_benign	0.129	benign	-0.39	Destabilizing	0.974	D	0.603	neutral	None	None	None	None	N
T/S	0.1373	likely_benign	0.1273	benign	-0.944	Destabilizing	0.062	N	0.304	neutral	N	0.400480372	None	None	N
T/V	0.1786	likely_benign	0.1647	benign	-0.378	Destabilizing	0.525	D	0.53	neutral	None	None	None	None	N
T/W	0.6201	likely_pathogenic	0.6315	pathogenic	-0.829	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
T/Y	0.3356	likely_benign	0.3371	benign	-0.546	Destabilizing	0.991	D	0.653	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.