TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25960	78103;78104;78105	chr2:178568254;178568253;178568252	chr2:179432981;179432980;179432979
N2AB	24319	73180;73181;73182	chr2:178568254;178568253;178568252	chr2:179432981;179432980;179432979
N2A	23392	70399;70400;70401	chr2:178568254;178568253;178568252	chr2:179432981;179432980;179432979
N2B	16895	50908;50909;50910	chr2:178568254;178568253;178568252	chr2:179432981;179432980;179432979
Novex-1	17020	51283;51284;51285	chr2:178568254;178568253;178568252	chr2:179432981;179432980;179432979
Novex-2	17087	51484;51485;51486	chr2:178568254;178568253;178568252	chr2:179432981;179432980;179432979
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: Fn3-76
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2992
• 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	rs367624488	-0.73	0.958	N	0.554	0.382	None	gnomAD-2.1.1	8.57E-05	None	None	None	None	N	None	9.51042E-04	2.83E-05	None	0	0	None	0	None	0	0	0
E/K	rs367624488	-0.73	0.958	N	0.554	0.382	None	gnomAD-3.1.2	2.56505E-04	None	None	None	None	N	None	9.17786E-04	6.56E-05	0	0	0	None	0	0	0	0	0
E/K	rs367624488	-0.73	0.958	N	0.554	0.382	None	gnomAD-4.0.0	4.95855E-05	None	None	None	None	N	None	1.02861E-03	5.00334E-05	None	0	0	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	0.2594	likely_benign	0.2747	benign	-1.063	Destabilizing	0.958	D	0.665	neutral	N	0.480638403	None	None	N
E/C	0.9295	likely_pathogenic	0.924	pathogenic	-0.582	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/D	0.6225	likely_pathogenic	0.579	pathogenic	-1.257	Destabilizing	0.067	N	0.213	neutral	N	0.468775118	None	None	N
E/F	0.9584	likely_pathogenic	0.9599	pathogenic	-0.67	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/G	0.5203	ambiguous	0.5524	ambiguous	-1.444	Destabilizing	0.988	D	0.755	deleterious	N	0.486665564	None	None	N
E/H	0.8559	likely_pathogenic	0.8456	pathogenic	-1.017	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/I	0.6047	likely_pathogenic	0.5869	pathogenic	-0.014	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
E/K	0.4382	ambiguous	0.4946	ambiguous	-0.895	Destabilizing	0.958	D	0.554	neutral	N	0.473508378	None	None	N
E/L	0.7067	likely_pathogenic	0.7152	pathogenic	-0.014	Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
E/M	0.6638	likely_pathogenic	0.6572	pathogenic	0.556	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/N	0.6697	likely_pathogenic	0.6491	pathogenic	-1.266	Destabilizing	0.982	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.7898	likely_pathogenic	0.7869	pathogenic	-0.344	Destabilizing	0.995	D	0.823	deleterious	None	None	None	None	N
E/Q	0.2382	likely_benign	0.2355	benign	-1.118	Destabilizing	0.994	D	0.671	neutral	N	0.516961436	None	None	N
E/R	0.613	likely_pathogenic	0.6276	pathogenic	-0.704	Destabilizing	0.995	D	0.749	deleterious	None	None	None	None	N
E/S	0.4149	ambiguous	0.4394	ambiguous	-1.682	Destabilizing	0.968	D	0.595	neutral	None	None	None	None	N
E/T	0.4275	ambiguous	0.4174	ambiguous	-1.36	Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	N
E/V	0.3854	ambiguous	0.3776	ambiguous	-0.344	Destabilizing	0.994	D	0.797	deleterious	N	0.521041891	None	None	N
E/W	0.9914	likely_pathogenic	0.991	pathogenic	-0.494	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.9314	likely_pathogenic	0.9272	pathogenic	-0.431	Destabilizing	1.0	D	0.794	deleterious	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.