TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13940	42043;42044;42045	chr2:178635506;178635505;178635504	chr2:179500233;179500232;179500231
N2AB	12299	37120;37121;37122	chr2:178635506;178635505;178635504	chr2:179500233;179500232;179500231
N2A	11372	34339;34340;34341	chr2:178635506;178635505;178635504	chr2:179500233;179500232;179500231
N2B	4875	14848;14849;14850	chr2:178635506;178635505;178635504	chr2:179500233;179500232;179500231
Novex-1	5000	15223;15224;15225	chr2:178635506;178635505;178635504	chr2:179500233;179500232;179500231
Novex-2	5067	15424;15425;15426	chr2:178635506;178635505;178635504	chr2:179500233;179500232;179500231
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-89
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.4313
• 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	None	None	0.002	N	0.18	0.058	0.119812018005	gnomAD-4.0.0	3.23387E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.80713E-06	0	0
E/Q	rs1172846357	0.129	0.791	N	0.44	0.169	0.183819452728	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/Q	rs1172846357	0.129	0.791	N	0.44	0.169	0.183819452728	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/Q	rs1172846357	0.129	0.791	N	0.44	0.169	0.183819452728	gnomAD-4.0.0	5.61401E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.66605E-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	0.2192	likely_benign	0.2376	benign	-0.215	Destabilizing	0.002	N	0.258	neutral	N	0.459229024	None	None	N
E/C	0.9457	likely_pathogenic	0.9623	pathogenic	-0.041	Destabilizing	0.995	D	0.523	neutral	None	None	None	None	N
E/D	0.1169	likely_benign	0.1484	benign	-0.21	Destabilizing	0.002	N	0.18	neutral	N	0.424420387	None	None	N
E/F	0.9354	likely_pathogenic	0.9486	pathogenic	-0.22	Destabilizing	0.946	D	0.535	neutral	None	None	None	None	N
E/G	0.2181	likely_benign	0.2658	benign	-0.37	Destabilizing	0.483	N	0.437	neutral	N	0.443071723	None	None	N
E/H	0.7538	likely_pathogenic	0.7855	pathogenic	0.185	Stabilizing	0.982	D	0.318	neutral	None	None	None	None	N
E/I	0.7095	likely_pathogenic	0.7323	pathogenic	0.146	Stabilizing	0.897	D	0.576	neutral	None	None	None	None	N
E/K	0.3856	ambiguous	0.3805	ambiguous	0.345	Stabilizing	0.651	D	0.441	neutral	N	0.459412465	None	None	N
E/L	0.7191	likely_pathogenic	0.7718	pathogenic	0.146	Stabilizing	0.712	D	0.507	neutral	None	None	None	None	N
E/M	0.7405	likely_pathogenic	0.7875	pathogenic	0.123	Stabilizing	0.995	D	0.469	neutral	None	None	None	None	N
E/N	0.3683	ambiguous	0.4214	ambiguous	0.167	Stabilizing	0.553	D	0.396	neutral	None	None	None	None	N
E/P	0.8329	likely_pathogenic	0.8648	pathogenic	0.045	Stabilizing	0.946	D	0.424	neutral	None	None	None	None	N
E/Q	0.293	likely_benign	0.3111	benign	0.182	Stabilizing	0.791	D	0.44	neutral	N	0.443340622	None	None	N
E/R	0.6026	likely_pathogenic	0.6259	pathogenic	0.564	Stabilizing	0.946	D	0.366	neutral	None	None	None	None	N
E/S	0.2441	likely_benign	0.2831	benign	-0.019	Destabilizing	0.338	N	0.372	neutral	None	None	None	None	N
E/T	0.3662	ambiguous	0.3947	ambiguous	0.107	Stabilizing	0.712	D	0.323	neutral	None	None	None	None	N
E/V	0.5009	ambiguous	0.5239	ambiguous	0.045	Stabilizing	0.483	N	0.437	neutral	N	0.445791187	None	None	N
E/W	0.9658	likely_pathogenic	0.9735	pathogenic	-0.135	Destabilizing	0.995	D	0.619	neutral	None	None	None	None	N
E/Y	0.8726	likely_pathogenic	0.8902	pathogenic	0.009	Stabilizing	0.982	D	0.48	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.