TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31386	94381;94382;94383	chr2:178547470;178547469;178547468	chr2:179412197;179412196;179412195
N2AB	29745	89458;89459;89460	chr2:178547470;178547469;178547468	chr2:179412197;179412196;179412195
N2A	28818	86677;86678;86679	chr2:178547470;178547469;178547468	chr2:179412197;179412196;179412195
N2B	22321	67186;67187;67188	chr2:178547470;178547469;178547468	chr2:179412197;179412196;179412195
Novex-1	22446	67561;67562;67563	chr2:178547470;178547469;178547468	chr2:179412197;179412196;179412195
Novex-2	22513	67762;67763;67764	chr2:178547470;178547469;178547468	chr2:179412197;179412196;179412195
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: Fn3-116
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2816
• 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/A	rs772833696	-0.741	0.999	N	0.707	0.369	0.403328974453	gnomAD-2.1.1	8.15E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.81E-05	0
E/A	rs772833696	-0.741	0.999	N	0.707	0.369	0.403328974453	gnomAD-4.0.0	6.16433E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.10104E-06	0	0
E/G	None	None	1.0	D	0.773	0.49	0.598035270499	gnomAD-4.0.0	1.36985E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80023E-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	0.8139	likely_pathogenic	0.7677	pathogenic	-0.562	Destabilizing	0.999	D	0.707	prob.neutral	N	0.511918189	None	None	I
E/C	0.9878	likely_pathogenic	0.9804	pathogenic	-0.514	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
E/D	0.9798	likely_pathogenic	0.9675	pathogenic	-1.255	Destabilizing	0.999	D	0.487	neutral	N	0.504121028	None	None	I
E/F	0.9965	likely_pathogenic	0.9944	pathogenic	-1.191	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
E/G	0.9082	likely_pathogenic	0.8874	pathogenic	-0.819	Destabilizing	1.0	D	0.773	deleterious	D	0.522225283	None	None	I
E/H	0.9877	likely_pathogenic	0.9795	pathogenic	-1.273	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/I	0.9477	likely_pathogenic	0.9084	pathogenic	0.107	Stabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
E/K	0.8296	likely_pathogenic	0.7851	pathogenic	-0.49	Destabilizing	0.999	D	0.573	neutral	N	0.472823589	None	None	I
E/L	0.9828	likely_pathogenic	0.9695	pathogenic	0.107	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
E/M	0.9513	likely_pathogenic	0.9255	pathogenic	0.471	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
E/N	0.9856	likely_pathogenic	0.9778	pathogenic	-0.65	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/P	0.9993	likely_pathogenic	0.9992	pathogenic	-0.096	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
E/Q	0.5256	ambiguous	0.4479	ambiguous	-0.576	Destabilizing	1.0	D	0.643	neutral	N	0.473873545	None	None	I
E/R	0.8906	likely_pathogenic	0.8619	pathogenic	-0.605	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
E/S	0.9159	likely_pathogenic	0.8768	pathogenic	-1.049	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
E/T	0.9263	likely_pathogenic	0.8884	pathogenic	-0.805	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
E/V	0.8514	likely_pathogenic	0.7565	pathogenic	-0.096	Destabilizing	1.0	D	0.835	deleterious	N	0.478741404	None	None	I
E/W	0.999	likely_pathogenic	0.9985	pathogenic	-1.444	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
E/Y	0.9952	likely_pathogenic	0.9927	pathogenic	-1.012	Destabilizing	1.0	D	0.868	deleterious	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.