TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6219	18880;18881;18882	chr2:178729501;178729500;178729499	chr2:179594228;179594227;179594226
N2AB	5902	17929;17930;17931	chr2:178729501;178729500;178729499	chr2:179594228;179594227;179594226
N2A	4975	15148;15149;15150	chr2:178729501;178729500;178729499	chr2:179594228;179594227;179594226
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-46
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5185
• 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
E/D	rs1282711943	-1.031	0.896	D	0.498	0.167	0.126345400529	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/D	rs1282711943	-1.031	0.896	D	0.498	0.167	0.126345400529	gnomAD-4.0.0	6.84296E-07	None	None	None	None	N	None	0	0	None	0	2.52003E-05	None	0	0	0	0	0
E/K	rs72648948	-0.522	0.896	N	0.496	0.178	None	gnomAD-2.1.1	5.72E-05	None	None	None	None	N	None	6.61704E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs72648948	-0.522	0.896	N	0.496	0.178	None	gnomAD-3.1.2	2.16917E-04	None	None	None	None	N	None	6.99773E-04	1.96618E-04	0	0	0	None	0	0	0	0	4.77555E-04
E/K	rs72648948	-0.522	0.896	N	0.496	0.178	None	gnomAD-4.0.0	3.03693E-05	None	None	None	None	N	None	6.00897E-04	5.00334E-05	None	0	0	None	0	0	0	0	1.60128E-05
E/Q	rs72648948	-0.708	0.984	N	0.568	0.293	0.37262878642	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
E/Q	rs72648948	-0.708	0.984	N	0.568	0.293	0.37262878642	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs72648948	-0.708	0.984	N	0.568	0.293	0.37262878642	gnomAD-4.0.0	3.71869E-06	None	None	None	None	N	None	5.34131E-05	0	None	0	2.22876E-05	None	0	0	0	0	1.60128E-05
E/V	rs2080005563	None	0.938	D	0.627	0.438	0.759310620552	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85927E-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
E/A	0.1145	likely_benign	0.1307	benign	-0.71	Destabilizing	0.811	D	0.531	neutral	N	0.487569342	None	None	N
E/C	0.7283	likely_pathogenic	0.7975	pathogenic	-0.457	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
E/D	0.2086	likely_benign	0.2585	benign	-1.275	Destabilizing	0.896	D	0.498	neutral	D	0.52218919	None	None	N
E/F	0.5936	likely_pathogenic	0.6506	pathogenic	-0.618	Destabilizing	0.988	D	0.713	prob.delet.	None	None	None	None	N
E/G	0.1663	likely_benign	0.1879	benign	-1.049	Destabilizing	0.026	N	0.447	neutral	N	0.494027803	None	None	N
E/H	0.3803	ambiguous	0.4284	ambiguous	-1.055	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	N
E/I	0.2324	likely_benign	0.2918	benign	0.201	Stabilizing	0.976	D	0.714	prob.delet.	None	None	None	None	N
E/K	0.1582	likely_benign	0.1705	benign	-0.79	Destabilizing	0.896	D	0.496	neutral	N	0.521495756	None	None	N
E/L	0.2851	likely_benign	0.34	ambiguous	0.201	Stabilizing	0.952	D	0.65	neutral	None	None	None	None	N
E/M	0.3424	ambiguous	0.3922	ambiguous	0.67	Stabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
E/N	0.2662	likely_benign	0.3386	benign	-1.046	Destabilizing	0.976	D	0.531	neutral	None	None	None	None	N
E/P	0.8276	likely_pathogenic	0.8473	pathogenic	-0.081	Destabilizing	0.988	D	0.645	neutral	None	None	None	None	N
E/Q	0.0983	likely_benign	0.1075	benign	-0.931	Destabilizing	0.984	D	0.568	neutral	N	0.499485688	None	None	N
E/R	0.2421	likely_benign	0.2458	benign	-0.69	Destabilizing	0.988	D	0.549	neutral	None	None	None	None	N
E/S	0.1606	likely_benign	0.1966	benign	-1.384	Destabilizing	0.851	D	0.479	neutral	None	None	None	None	N
E/T	0.1486	likely_benign	0.1848	benign	-1.11	Destabilizing	0.132	N	0.415	neutral	None	None	None	None	N
E/V	0.1453	likely_benign	0.1764	benign	-0.081	Destabilizing	0.938	D	0.627	neutral	D	0.531752822	None	None	N
E/W	0.8324	likely_pathogenic	0.8474	pathogenic	-0.588	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/Y	0.5452	ambiguous	0.6078	pathogenic	-0.427	Destabilizing	0.996	D	0.701	prob.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.