TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8462	25609;25610;25611	chr2:178717350;178717349;178717348	chr2:179582077;179582076;179582075
N2AB	8145	24658;24659;24660	chr2:178717350;178717349;178717348	chr2:179582077;179582076;179582075
N2A	7218	21877;21878;21879	chr2:178717350;178717349;178717348	chr2:179582077;179582076;179582075
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-70
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2501
• 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
P/H	rs1249885767	-1.095	0.999	N	0.705	0.386	0.422404719673	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	0	0	None	0	2.05002E-04	None	0	None	0	0	0
P/H	rs1249885767	-1.095	0.999	N	0.705	0.386	0.422404719673	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	5.77145E-04	None	0	0	0	0	0
P/H	rs1249885767	-1.095	0.999	N	0.705	0.386	0.422404719673	gnomAD-4.0.0	4.96379E-06	None	None	None	None	I	None	0	0	None	0	1.56118E-04	None	0	0	0	0	1.60303E-05
P/S	None	None	0.878	N	0.59	0.303	0.188950314367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.2529	likely_benign	0.1338	benign	-1.587	Destabilizing	0.053	N	0.385	neutral	N	0.470534821	None	None	I
P/C	0.9421	likely_pathogenic	0.8792	pathogenic	-0.967	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	I
P/D	0.9906	likely_pathogenic	0.9801	pathogenic	-1.331	Destabilizing	0.905	D	0.663	neutral	None	None	None	None	I
P/E	0.9714	likely_pathogenic	0.9411	pathogenic	-1.217	Destabilizing	0.938	D	0.656	neutral	None	None	None	None	I
P/F	0.9844	likely_pathogenic	0.9652	pathogenic	-0.966	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	I
P/G	0.8842	likely_pathogenic	0.7326	pathogenic	-2.033	Highly Destabilizing	0.932	D	0.624	neutral	None	None	None	None	I
P/H	0.9771	likely_pathogenic	0.9534	pathogenic	-1.638	Destabilizing	0.999	D	0.705	prob.neutral	N	0.506200353	None	None	I
P/I	0.8162	likely_pathogenic	0.7283	pathogenic	-0.41	Destabilizing	0.679	D	0.489	neutral	None	None	None	None	I
P/K	0.9915	likely_pathogenic	0.9824	pathogenic	-1.166	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	I
P/L	0.3965	ambiguous	0.3128	benign	-0.41	Destabilizing	0.063	N	0.455	neutral	N	0.457053836	None	None	I
P/M	0.8212	likely_pathogenic	0.7265	pathogenic	-0.31	Destabilizing	0.989	D	0.728	prob.delet.	None	None	None	None	I
P/N	0.9794	likely_pathogenic	0.9505	pathogenic	-1.139	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
P/Q	0.9549	likely_pathogenic	0.9116	pathogenic	-1.124	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	I
P/R	0.9769	likely_pathogenic	0.9555	pathogenic	-0.896	Destabilizing	0.997	D	0.709	prob.delet.	N	0.512276739	None	None	I
P/S	0.8493	likely_pathogenic	0.6668	pathogenic	-1.799	Destabilizing	0.878	D	0.59	neutral	N	0.478688349	None	None	I
P/T	0.6496	likely_pathogenic	0.4693	ambiguous	-1.55	Destabilizing	0.865	D	0.591	neutral	N	0.49662802	None	None	I
P/V	0.6269	likely_pathogenic	0.4905	ambiguous	-0.769	Destabilizing	0.711	D	0.547	neutral	None	None	None	None	I
P/W	0.9968	likely_pathogenic	0.9916	pathogenic	-1.311	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/Y	0.9907	likely_pathogenic	0.978	pathogenic	-0.944	Destabilizing	0.998	D	0.782	deleterious	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.