TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7876	23851;23852;23853	chr2:178720016;178720015;178720014	chr2:179584743;179584742;179584741
N2AB	7559	22900;22901;22902	chr2:178720016;178720015;178720014	chr2:179584743;179584742;179584741
N2A	6632	20119;20120;20121	chr2:178720016;178720015;178720014	chr2:179584743;179584742;179584741
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-63
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.6299
• Predicted PPI site: I

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
M/I	None	None	None	N	0.137	0.193	0.53104733087	gnomAD-4.0.0	3.19068E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41663E-04	2.86587E-06	0	0
M/V	None	None	0.005	N	0.188	0.106	0.52633505579	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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
M/A	0.3414	ambiguous	0.3518	ambiguous	-1.068	Destabilizing	0.007	N	0.272	neutral	None	None	None	None	I
M/C	0.8174	likely_pathogenic	0.7834	pathogenic	-0.839	Destabilizing	0.356	N	0.49	neutral	None	None	None	None	I
M/D	0.7711	likely_pathogenic	0.7778	pathogenic	-0.216	Destabilizing	0.031	N	0.566	neutral	None	None	None	None	I
M/E	0.3952	ambiguous	0.3961	ambiguous	-0.243	Destabilizing	0.016	N	0.481	neutral	None	None	None	None	I
M/F	0.3026	likely_benign	0.2895	benign	-0.399	Destabilizing	0.136	N	0.432	neutral	None	None	None	None	I
M/G	0.5418	ambiguous	0.5264	ambiguous	-1.297	Destabilizing	0.031	N	0.571	neutral	None	None	None	None	I
M/H	0.5049	ambiguous	0.5246	ambiguous	-0.345	Destabilizing	0.356	N	0.526	neutral	None	None	None	None	I
M/I	0.277	likely_benign	0.2637	benign	-0.528	Destabilizing	None	N	0.137	neutral	N	0.49630931	None	None	I
M/K	0.218	likely_benign	0.2311	benign	-0.126	Destabilizing	None	N	0.173	neutral	N	0.428676022	None	None	I
M/L	0.1331	likely_benign	0.1364	benign	-0.528	Destabilizing	0.002	N	0.203	neutral	N	0.511854766	None	None	I
M/N	0.4014	ambiguous	0.4024	ambiguous	0.03	Stabilizing	0.072	N	0.559	neutral	None	None	None	None	I
M/P	0.8955	likely_pathogenic	0.8994	pathogenic	-0.68	Destabilizing	0.136	N	0.564	neutral	None	None	None	None	I
M/Q	0.2191	likely_benign	0.2262	benign	-0.138	Destabilizing	0.001	N	0.13	neutral	None	None	None	None	I
M/R	0.2281	likely_benign	0.2467	benign	0.458	Stabilizing	0.012	N	0.471	neutral	N	0.500117619	None	None	I
M/S	0.293	likely_benign	0.2895	benign	-0.465	Destabilizing	0.016	N	0.375	neutral	None	None	None	None	I
M/T	0.1811	likely_benign	0.1742	benign	-0.392	Destabilizing	None	N	0.166	neutral	N	0.434047343	None	None	I
M/V	0.0986	likely_benign	0.0914	benign	-0.68	Destabilizing	0.005	N	0.188	neutral	N	0.484110804	None	None	I
M/W	0.5993	likely_pathogenic	0.6051	pathogenic	-0.32	Destabilizing	0.864	D	0.484	neutral	None	None	None	None	I
M/Y	0.5454	ambiguous	0.5605	ambiguous	-0.281	Destabilizing	0.136	N	0.512	neutral	None	None	None	None	I

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.