TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28226	84901;84902;84903	chr2:178561456;178561455;178561454	chr2:179426183;179426182;179426181
N2AB	26585	79978;79979;79980	chr2:178561456;178561455;178561454	chr2:179426183;179426182;179426181
N2A	25658	77197;77198;77199	chr2:178561456;178561455;178561454	chr2:179426183;179426182;179426181
N2B	19161	57706;57707;57708	chr2:178561456;178561455;178561454	chr2:179426183;179426182;179426181
Novex-1	19286	58081;58082;58083	chr2:178561456;178561455;178561454	chr2:179426183;179426182;179426181
Novex-2	19353	58282;58283;58284	chr2:178561456;178561455;178561454	chr2:179426183;179426182;179426181
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: Fn3-93
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2044
• 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	rs2154159665	None	0.698	N	0.66	0.262	0.290962096972	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
E/K	rs2154159665	None	0.698	N	0.66	0.262	0.290962096972	gnomAD-4.0.0	2.02963E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.20494E-06	4.69704E-05	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	0.6365	likely_pathogenic	0.6067	pathogenic	-1.509	Destabilizing	0.822	D	0.605	neutral	N	0.498262132	None	None	N
E/C	0.9553	likely_pathogenic	0.9567	pathogenic	-0.917	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
E/D	0.7733	likely_pathogenic	0.7386	pathogenic	-1.754	Destabilizing	0.656	D	0.62	neutral	N	0.494249661	None	None	N
E/F	0.9789	likely_pathogenic	0.9766	pathogenic	-1.109	Destabilizing	0.978	D	0.74	deleterious	None	None	None	None	N
E/G	0.7861	likely_pathogenic	0.7565	pathogenic	-1.931	Destabilizing	0.822	D	0.574	neutral	D	0.52873665	None	None	N
E/H	0.9322	likely_pathogenic	0.9273	pathogenic	-1.21	Destabilizing	0.043	N	0.496	neutral	None	None	None	None	N
E/I	0.8511	likely_pathogenic	0.8426	pathogenic	-0.302	Destabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	N
E/K	0.8101	likely_pathogenic	0.8012	pathogenic	-1.705	Destabilizing	0.698	D	0.66	neutral	N	0.470990391	None	None	N
E/L	0.9227	likely_pathogenic	0.9069	pathogenic	-0.302	Destabilizing	0.86	D	0.652	neutral	None	None	None	None	N
E/M	0.8566	likely_pathogenic	0.8452	pathogenic	0.471	Stabilizing	0.994	D	0.69	prob.neutral	None	None	None	None	N
E/N	0.8941	likely_pathogenic	0.8774	pathogenic	-1.995	Destabilizing	0.86	D	0.573	neutral	None	None	None	None	N
E/P	0.9988	likely_pathogenic	0.9986	pathogenic	-0.689	Destabilizing	0.978	D	0.613	neutral	None	None	None	None	N
E/Q	0.3157	likely_benign	0.3092	benign	-1.678	Destabilizing	0.058	N	0.303	neutral	N	0.481214067	None	None	N
E/R	0.8664	likely_pathogenic	0.8542	pathogenic	-1.516	Destabilizing	0.754	D	0.576	neutral	None	None	None	None	N
E/S	0.6557	likely_pathogenic	0.6196	pathogenic	-2.631	Highly Destabilizing	0.86	D	0.609	neutral	None	None	None	None	N
E/T	0.7291	likely_pathogenic	0.7005	pathogenic	-2.241	Highly Destabilizing	0.86	D	0.578	neutral	None	None	None	None	N
E/V	0.7083	likely_pathogenic	0.696	pathogenic	-0.689	Destabilizing	0.942	D	0.643	neutral	N	0.47124388	None	None	N
E/W	0.9951	likely_pathogenic	0.9945	pathogenic	-1.162	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
E/Y	0.9712	likely_pathogenic	0.9692	pathogenic	-0.944	Destabilizing	0.956	D	0.677	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.