TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17072	51439;51440;51441	chr2:178610312;178610311;178610310	chr2:179475039;179475038;179475037
N2AB	15431	46516;46517;46518	chr2:178610312;178610311;178610310	chr2:179475039;179475038;179475037
N2A	14504	43735;43736;43737	chr2:178610312;178610311;178610310	chr2:179475039;179475038;179475037
N2B	8007	24244;24245;24246	chr2:178610312;178610311;178610310	chr2:179475039;179475038;179475037
Novex-1	8132	24619;24620;24621	chr2:178610312;178610311;178610310	chr2:179475039;179475038;179475037
Novex-2	8199	24820;24821;24822	chr2:178610312;178610311;178610310	chr2:179475039;179475038;179475037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-12
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8465
• 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
E/Q	rs1374988000	0.042	0.946	N	0.485	0.199	0.334161072951	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/Q	rs1374988000	0.042	0.946	N	0.485	0.199	0.334161072951	gnomAD-4.0.0	3.18644E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86223E-06	0	3.02939E-05

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	0.1366	likely_benign	0.1414	benign	-0.081	Destabilizing	0.896	D	0.547	neutral	N	0.473115746	None	None	I
E/C	0.8242	likely_pathogenic	0.8418	pathogenic	-0.344	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
E/D	0.0862	likely_benign	0.0857	benign	-0.328	Destabilizing	0.004	N	0.151	neutral	N	0.462293107	None	None	I
E/F	0.781	likely_pathogenic	0.8066	pathogenic	-0.048	Destabilizing	0.996	D	0.629	neutral	None	None	None	None	I
E/G	0.215	likely_benign	0.238	benign	-0.208	Destabilizing	0.896	D	0.549	neutral	N	0.472636662	None	None	I
E/H	0.5439	ambiguous	0.5587	ambiguous	0.597	Stabilizing	0.996	D	0.499	neutral	None	None	None	None	I
E/I	0.2904	likely_benign	0.2991	benign	0.199	Stabilizing	0.988	D	0.633	neutral	None	None	None	None	I
E/K	0.2555	likely_benign	0.2815	benign	0.318	Stabilizing	0.896	D	0.53	neutral	N	0.466360353	None	None	I
E/L	0.3301	likely_benign	0.3429	ambiguous	0.199	Stabilizing	0.988	D	0.631	neutral	None	None	None	None	I
E/M	0.4626	ambiguous	0.4677	ambiguous	-0.092	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
E/N	0.2135	likely_benign	0.2322	benign	0.017	Stabilizing	0.851	D	0.513	neutral	None	None	None	None	I
E/P	0.4421	ambiguous	0.4683	ambiguous	0.123	Stabilizing	0.988	D	0.495	neutral	None	None	None	None	I
E/Q	0.1931	likely_benign	0.1952	benign	0.036	Stabilizing	0.946	D	0.485	neutral	N	0.471843009	None	None	I
E/R	0.3917	ambiguous	0.4211	ambiguous	0.62	Stabilizing	0.988	D	0.501	neutral	None	None	None	None	I
E/S	0.1769	likely_benign	0.195	benign	-0.122	Destabilizing	0.919	D	0.505	neutral	None	None	None	None	I
E/T	0.2115	likely_benign	0.2164	benign	-0.01	Destabilizing	0.959	D	0.506	neutral	None	None	None	None	I
E/V	0.1777	likely_benign	0.1823	benign	0.123	Stabilizing	0.984	D	0.541	neutral	N	0.484508233	None	None	I
E/W	0.9216	likely_pathogenic	0.9345	pathogenic	0.025	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
E/Y	0.6359	likely_pathogenic	0.674	pathogenic	0.177	Stabilizing	0.996	D	0.603	neutral	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.