TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8222	24889;24890;24891	chr2:178718442;178718441;178718440	chr2:179583169;179583168;179583167
N2AB	7905	23938;23939;23940	chr2:178718442;178718441;178718440	chr2:179583169;179583168;179583167
N2A	6978	21157;21158;21159	chr2:178718442;178718441;178718440	chr2:179583169;179583168;179583167
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-67
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4345
• 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/I	None	None	0.994	D	0.322	0.357	0.482283251092	gnomAD-4.0.0	6.84228E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-07	0	0
T/R	None	None	0.994	D	0.324	0.336	0.532842626647	gnomAD-4.0.0	6.84228E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-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
T/A	0.2934	likely_benign	0.2712	benign	-0.518	Destabilizing	0.116	N	0.125	neutral	N	0.493632502	None	None	N
T/C	0.9202	likely_pathogenic	0.8924	pathogenic	-0.305	Destabilizing	1.0	D	0.332	neutral	None	None	None	None	N
T/D	0.6483	likely_pathogenic	0.6026	pathogenic	0.221	Stabilizing	0.969	D	0.326	neutral	None	None	None	None	N
T/E	0.654	likely_pathogenic	0.6429	pathogenic	0.173	Stabilizing	0.969	D	0.287	neutral	None	None	None	None	N
T/F	0.7975	likely_pathogenic	0.7878	pathogenic	-0.871	Destabilizing	0.999	D	0.415	neutral	None	None	None	None	N
T/G	0.4429	ambiguous	0.4032	ambiguous	-0.697	Destabilizing	0.969	D	0.335	neutral	None	None	None	None	N
T/H	0.7104	likely_pathogenic	0.651	pathogenic	-0.949	Destabilizing	1.0	D	0.414	neutral	None	None	None	None	N
T/I	0.7969	likely_pathogenic	0.8102	pathogenic	-0.159	Destabilizing	0.994	D	0.322	neutral	D	0.527480366	None	None	N
T/K	0.5669	likely_pathogenic	0.5219	ambiguous	-0.457	Destabilizing	0.959	D	0.309	neutral	N	0.482134384	None	None	N
T/L	0.3496	ambiguous	0.3415	ambiguous	-0.159	Destabilizing	0.969	D	0.305	neutral	None	None	None	None	N
T/M	0.2077	likely_benign	0.1991	benign	-0.017	Destabilizing	1.0	D	0.327	neutral	None	None	None	None	N
T/N	0.2628	likely_benign	0.2283	benign	-0.29	Destabilizing	0.969	D	0.266	neutral	None	None	None	None	N
T/P	0.646	likely_pathogenic	0.6328	pathogenic	-0.248	Destabilizing	0.068	N	0.233	neutral	N	0.488316584	None	None	N
T/Q	0.5656	likely_pathogenic	0.5224	ambiguous	-0.463	Destabilizing	0.995	D	0.333	neutral	None	None	None	None	N
T/R	0.5133	ambiguous	0.4782	ambiguous	-0.197	Destabilizing	0.994	D	0.324	neutral	D	0.535059699	None	None	N
T/S	0.27	likely_benign	0.2103	benign	-0.535	Destabilizing	0.476	N	0.199	neutral	D	0.532750113	None	None	N
T/V	0.628	likely_pathogenic	0.6379	pathogenic	-0.248	Destabilizing	0.969	D	0.225	neutral	None	None	None	None	N
T/W	0.9308	likely_pathogenic	0.915	pathogenic	-0.862	Destabilizing	1.0	D	0.522	neutral	None	None	None	None	N
T/Y	0.8165	likely_pathogenic	0.7918	pathogenic	-0.597	Destabilizing	0.999	D	0.411	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.