TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28759	86500;86501;86502	chr2:178559857;178559856;178559855	chr2:179424584;179424583;179424582
N2AB	27118	81577;81578;81579	chr2:178559857;178559856;178559855	chr2:179424584;179424583;179424582
N2A	26191	78796;78797;78798	chr2:178559857;178559856;178559855	chr2:179424584;179424583;179424582
N2B	19694	59305;59306;59307	chr2:178559857;178559856;178559855	chr2:179424584;179424583;179424582
Novex-1	19819	59680;59681;59682	chr2:178559857;178559856;178559855	chr2:179424584;179424583;179424582
Novex-2	19886	59881;59882;59883	chr2:178559857;178559856;178559855	chr2:179424584;179424583;179424582
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: Ig-144
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5742
• 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/K	rs1180434242	0.361	0.722	N	0.527	0.221	0.302459207581	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/K	rs1180434242	0.361	0.722	N	0.527	0.221	0.302459207581	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1180434242	0.361	0.722	N	0.527	0.221	0.302459207581	gnomAD-4.0.0	2.56881E-06	None	None	None	None	N	None	1.69125E-05	0	None	0	2.42448E-05	None	0	0	0	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	0.262	likely_benign	0.2106	benign	-0.279	Destabilizing	0.722	D	0.49	neutral	N	0.504155215	None	None	N
E/C	0.9181	likely_pathogenic	0.8824	pathogenic	0.018	Stabilizing	0.996	D	0.664	neutral	None	None	None	None	N
E/D	0.1217	likely_benign	0.0956	benign	-0.201	Destabilizing	0.003	N	0.299	neutral	N	0.44622442	None	None	N
E/F	0.8774	likely_pathogenic	0.8117	pathogenic	-0.274	Destabilizing	0.987	D	0.631	neutral	None	None	None	None	N
E/G	0.2664	likely_benign	0.2042	benign	-0.446	Destabilizing	0.565	D	0.501	neutral	N	0.483789771	None	None	N
E/H	0.6434	likely_pathogenic	0.5408	ambiguous	0.043	Stabilizing	0.961	D	0.466	neutral	None	None	None	None	N
E/I	0.6303	likely_pathogenic	0.5175	ambiguous	0.116	Stabilizing	0.961	D	0.636	neutral	None	None	None	None	N
E/K	0.2996	likely_benign	0.2313	benign	0.35	Stabilizing	0.722	D	0.527	neutral	N	0.497613245	None	None	N
E/L	0.6273	likely_pathogenic	0.5254	ambiguous	0.116	Stabilizing	0.961	D	0.619	neutral	None	None	None	None	N
E/M	0.6521	likely_pathogenic	0.5718	pathogenic	0.172	Stabilizing	0.996	D	0.599	neutral	None	None	None	None	N
E/N	0.3323	likely_benign	0.2536	benign	0.157	Stabilizing	0.024	N	0.338	neutral	None	None	None	None	N
E/P	0.7883	likely_pathogenic	0.6711	pathogenic	0.004	Stabilizing	0.961	D	0.484	neutral	None	None	None	None	N
E/Q	0.244	likely_benign	0.2041	benign	0.177	Stabilizing	0.901	D	0.457	neutral	N	0.507483522	None	None	N
E/R	0.4845	ambiguous	0.3955	ambiguous	0.539	Stabilizing	0.923	D	0.463	neutral	None	None	None	None	N
E/S	0.2712	likely_benign	0.2101	benign	-0.027	Destabilizing	0.633	D	0.509	neutral	None	None	None	None	N
E/T	0.3484	ambiguous	0.273	benign	0.107	Stabilizing	0.775	D	0.459	neutral	None	None	None	None	N
E/V	0.4097	ambiguous	0.3213	benign	0.004	Stabilizing	0.949	D	0.566	neutral	N	0.49556415	None	None	N
E/W	0.9552	likely_pathogenic	0.9263	pathogenic	-0.176	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
E/Y	0.7882	likely_pathogenic	0.6992	pathogenic	-0.043	Destabilizing	0.987	D	0.583	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.