TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27011	81256;81257;81258	chr2:178565101;178565100;178565099	chr2:179429828;179429827;179429826
N2AB	25370	76333;76334;76335	chr2:178565101;178565100;178565099	chr2:179429828;179429827;179429826
N2A	24443	73552;73553;73554	chr2:178565101;178565100;178565099	chr2:179429828;179429827;179429826
N2B	17946	54061;54062;54063	chr2:178565101;178565100;178565099	chr2:179429828;179429827;179429826
Novex-1	18071	54436;54437;54438	chr2:178565101;178565100;178565099	chr2:179429828;179429827;179429826
Novex-2	18138	54637;54638;54639	chr2:178565101;178565100;178565099	chr2:179429828;179429827;179429826
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: Fn3-84
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.0921
• 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/D	rs765653425	-1.868	0.996	N	0.638	0.329	0.28492961333	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/D	rs765653425	-1.868	0.996	N	0.638	0.329	0.28492961333	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	3.16456E-03	1.47E-05	0	0
E/D	rs765653425	-1.868	0.996	N	0.638	0.329	0.28492961333	gnomAD-4.0.0	6.84294E-07	None	None	None	None	N	None	2.98918E-05	0	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	0.4879	ambiguous	0.4566	ambiguous	-0.701	Destabilizing	0.996	D	0.667	neutral	D	0.5323935	None	None	N
E/C	0.9124	likely_pathogenic	0.9143	pathogenic	-0.028	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/D	0.6927	likely_pathogenic	0.6721	pathogenic	-1.572	Destabilizing	0.996	D	0.638	neutral	N	0.471586275	None	None	N
E/F	0.9236	likely_pathogenic	0.937	pathogenic	-0.461	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/G	0.6233	likely_pathogenic	0.6116	pathogenic	-1.093	Destabilizing	0.999	D	0.763	deleterious	D	0.522647037	None	None	N
E/H	0.7956	likely_pathogenic	0.8407	pathogenic	-0.379	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/I	0.8288	likely_pathogenic	0.8133	pathogenic	0.415	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/K	0.6734	likely_pathogenic	0.6839	pathogenic	-0.735	Destabilizing	0.992	D	0.653	neutral	N	0.519605163	None	None	N
E/L	0.6662	likely_pathogenic	0.6714	pathogenic	0.415	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/M	0.6589	likely_pathogenic	0.6369	pathogenic	0.977	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/N	0.8158	likely_pathogenic	0.8043	pathogenic	-1.093	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/P	0.9988	likely_pathogenic	0.9991	pathogenic	0.059	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/Q	0.2272	likely_benign	0.2097	benign	-0.746	Destabilizing	0.957	D	0.395	neutral	N	0.508725955	None	None	N
E/R	0.8113	likely_pathogenic	0.8251	pathogenic	-0.776	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
E/S	0.5903	likely_pathogenic	0.5602	ambiguous	-1.595	Destabilizing	0.997	D	0.697	prob.neutral	None	None	None	None	N
E/T	0.7756	likely_pathogenic	0.7432	pathogenic	-1.213	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/V	0.6536	likely_pathogenic	0.6246	pathogenic	0.059	Stabilizing	0.999	D	0.787	deleterious	N	0.518012228	None	None	N
E/W	0.9773	likely_pathogenic	0.9837	pathogenic	-0.698	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/Y	0.8865	likely_pathogenic	0.9069	pathogenic	-0.284	Destabilizing	1.0	D	0.822	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.