TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6721	20386;20387;20388	chr2:178727204;178727203;178727202	chr2:179591931;179591930;179591929
N2AB	6404	19435;19436;19437	chr2:178727204;178727203;178727202	chr2:179591931;179591930;179591929
N2A	5477	16654;16655;16656	chr2:178727204;178727203;178727202	chr2:179591931;179591930;179591929
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-51
• Domain position: 55
• Structural Position: 134
• Q(SASA): 0.3029
• 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
S/L	None	None	0.027	N	0.43	0.377	0.6450407448	gnomAD-4.0.0	6.84445E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9973E-07	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
S/A	0.0997	likely_benign	0.0902	benign	-0.443	Destabilizing	0.068	N	0.405	neutral	N	0.49043927	None	None	N
S/C	0.2628	likely_benign	0.2387	benign	-0.305	Destabilizing	0.996	D	0.459	neutral	None	None	None	None	N
S/D	0.4976	ambiguous	0.4985	ambiguous	0.323	Stabilizing	0.613	D	0.434	neutral	None	None	None	None	N
S/E	0.672	likely_pathogenic	0.6618	pathogenic	0.357	Stabilizing	0.816	D	0.432	neutral	None	None	None	None	N
S/F	0.3274	likely_benign	0.3113	benign	-0.64	Destabilizing	0.079	N	0.437	neutral	None	None	None	None	N
S/G	0.1048	likely_benign	0.1117	benign	-0.71	Destabilizing	0.855	D	0.368	neutral	None	None	None	None	N
S/H	0.4604	ambiguous	0.4737	ambiguous	-1.079	Destabilizing	0.988	D	0.46	neutral	None	None	None	None	N
S/I	0.5102	ambiguous	0.4899	ambiguous	0.159	Stabilizing	0.856	D	0.524	neutral	None	None	None	None	N
S/K	0.7701	likely_pathogenic	0.7866	pathogenic	-0.247	Destabilizing	0.922	D	0.436	neutral	None	None	None	None	N
S/L	0.1472	likely_benign	0.1416	benign	0.159	Stabilizing	0.027	N	0.43	neutral	N	0.504837449	None	None	N
S/M	0.2747	likely_benign	0.2644	benign	0.073	Stabilizing	0.977	D	0.465	neutral	None	None	None	None	N
S/N	0.2127	likely_benign	0.2127	benign	-0.342	Destabilizing	0.005	N	0.24	neutral	None	None	None	None	N
S/P	0.6462	likely_pathogenic	0.6647	pathogenic	-0.006	Destabilizing	0.981	D	0.491	neutral	N	0.50871179	None	None	N
S/Q	0.6133	likely_pathogenic	0.6034	pathogenic	-0.332	Destabilizing	0.988	D	0.497	neutral	None	None	None	None	N
S/R	0.7167	likely_pathogenic	0.7347	pathogenic	-0.297	Destabilizing	0.988	D	0.491	neutral	None	None	None	None	N
S/T	0.1148	likely_benign	0.1145	benign	-0.328	Destabilizing	0.004	N	0.235	neutral	D	0.522938551	None	None	N
S/V	0.4102	ambiguous	0.3815	ambiguous	-0.006	Destabilizing	0.689	D	0.515	neutral	None	None	None	None	N
S/W	0.4983	ambiguous	0.4926	ambiguous	-0.713	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
S/Y	0.2516	likely_benign	0.2509	benign	-0.359	Destabilizing	0.954	D	0.571	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.