TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35763	107512;107513;107514	chr2:178528364;178528363;178528362	chr2:179393091;179393090;179393089
N2AB	34122	102589;102590;102591	chr2:178528364;178528363;178528362	chr2:179393091;179393090;179393089
N2A	33195	99808;99809;99810	chr2:178528364;178528363;178528362	chr2:179393091;179393090;179393089
N2B	26698	80317;80318;80319	chr2:178528364;178528363;178528362	chr2:179393091;179393090;179393089
Novex-1	26823	80692;80693;80694	chr2:178528364;178528363;178528362	chr2:179393091;179393090;179393089
Novex-2	26890	80893;80894;80895	chr2:178528364;178528363;178528362	chr2:179393091;179393090;179393089
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-168
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.6462
• 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
N/K	None	None	0.004	N	0.305	0.068	0.0666544352282	gnomAD-4.0.0	1.591E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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
N/A	0.4587	ambiguous	0.4558	ambiguous	-0.356	Destabilizing	0.25	N	0.323	neutral	None	None	None	None	N
N/C	0.6263	likely_pathogenic	0.6186	pathogenic	0.496	Stabilizing	0.992	D	0.455	neutral	None	None	None	None	N
N/D	0.1512	likely_benign	0.1415	benign	-0.191	Destabilizing	0.379	N	0.279	neutral	N	0.484453868	None	None	N
N/E	0.452	ambiguous	0.4383	ambiguous	-0.226	Destabilizing	0.021	N	0.299	neutral	None	None	None	None	N
N/F	0.7697	likely_pathogenic	0.7893	pathogenic	-0.708	Destabilizing	0.92	D	0.425	neutral	None	None	None	None	N
N/G	0.3757	ambiguous	0.3802	ambiguous	-0.539	Destabilizing	0.25	N	0.26	neutral	None	None	None	None	N
N/H	0.1555	likely_benign	0.1615	benign	-0.633	Destabilizing	0.009	N	0.283	neutral	N	0.514528846	None	None	N
N/I	0.6495	likely_pathogenic	0.6477	pathogenic	0.043	Stabilizing	0.896	D	0.435	neutral	N	0.484968999	None	None	N
N/K	0.3426	ambiguous	0.3154	benign	0.103	Stabilizing	0.004	N	0.305	neutral	N	0.491342555	None	None	N
N/L	0.5213	ambiguous	0.5359	ambiguous	0.043	Stabilizing	0.617	D	0.373	neutral	None	None	None	None	N
N/M	0.5909	likely_pathogenic	0.5978	pathogenic	0.606	Stabilizing	0.992	D	0.395	neutral	None	None	None	None	N
N/P	0.9257	likely_pathogenic	0.9285	pathogenic	-0.064	Destabilizing	0.92	D	0.393	neutral	None	None	None	None	N
N/Q	0.423	ambiguous	0.4198	ambiguous	-0.38	Destabilizing	0.447	N	0.331	neutral	None	None	None	None	N
N/R	0.4314	ambiguous	0.4186	ambiguous	0.21	Stabilizing	0.447	N	0.341	neutral	None	None	None	None	N
N/S	0.144	likely_benign	0.1444	benign	-0.084	Destabilizing	0.007	N	0.189	neutral	N	0.461001005	None	None	N
N/T	0.3519	ambiguous	0.3404	ambiguous	0.017	Stabilizing	0.379	N	0.253	neutral	N	0.463382024	None	None	N
N/V	0.6414	likely_pathogenic	0.6465	pathogenic	-0.064	Destabilizing	0.85	D	0.396	neutral	None	None	None	None	N
N/W	0.8986	likely_pathogenic	0.9043	pathogenic	-0.667	Destabilizing	0.992	D	0.557	neutral	None	None	None	None	N
N/Y	0.269	likely_benign	0.2749	benign	-0.406	Destabilizing	0.81	D	0.404	neutral	N	0.475245309	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.