TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27317	82174;82175;82176	chr2:178564183;178564182;178564181	chr2:179428910;179428909;179428908
N2AB	25676	77251;77252;77253	chr2:178564183;178564182;178564181	chr2:179428910;179428909;179428908
N2A	24749	74470;74471;74472	chr2:178564183;178564182;178564181	chr2:179428910;179428909;179428908
N2B	18252	54979;54980;54981	chr2:178564183;178564182;178564181	chr2:179428910;179428909;179428908
Novex-1	18377	55354;55355;55356	chr2:178564183;178564182;178564181	chr2:179428910;179428909;179428908
Novex-2	18444	55555;55556;55557	chr2:178564183;178564182;178564181	chr2:179428910;179428909;179428908
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-140
• Domain position: 40
• Structural Position: 69
• Q(SASA): 0.6571
• 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/Q	rs1434330338	-0.034	0.989	D	0.515	0.274	0.437634105008	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/Q	rs1434330338	-0.034	0.989	D	0.515	0.274	0.437634105008	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1434330338	-0.034	0.989	D	0.515	0.274	0.437634105008	gnomAD-4.0.0	3.09867E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.3905E-06	1.09789E-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	0.1144	likely_benign	0.1132	benign	-0.05	Destabilizing	0.989	D	0.563	neutral	N	0.490730132	None	None	N
E/C	0.6838	likely_pathogenic	0.6871	pathogenic	-0.043	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/D	0.1023	likely_benign	0.1056	benign	-0.258	Destabilizing	0.054	N	0.213	neutral	N	0.464122321	None	None	N
E/F	0.5651	likely_pathogenic	0.5818	pathogenic	-0.071	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
E/G	0.0968	likely_benign	0.0958	benign	-0.19	Destabilizing	0.978	D	0.547	neutral	D	0.528037726	None	None	N
E/H	0.3303	likely_benign	0.3321	benign	0.399	Stabilizing	0.999	D	0.549	neutral	None	None	None	None	N
E/I	0.2368	likely_benign	0.2382	benign	0.264	Stabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
E/K	0.1001	likely_benign	0.1038	benign	0.481	Stabilizing	0.978	D	0.558	neutral	N	0.496423953	None	None	N
E/L	0.2304	likely_benign	0.2297	benign	0.264	Stabilizing	0.998	D	0.664	neutral	None	None	None	None	N
E/M	0.3204	likely_benign	0.3181	benign	0.124	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/N	0.1903	likely_benign	0.1899	benign	0.232	Stabilizing	0.983	D	0.525	neutral	None	None	None	None	N
E/P	0.2903	likely_benign	0.2834	benign	0.178	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	N
E/Q	0.1134	likely_benign	0.1111	benign	0.251	Stabilizing	0.989	D	0.515	neutral	D	0.534808983	None	None	N
E/R	0.1737	likely_benign	0.1811	benign	0.675	Stabilizing	0.998	D	0.557	neutral	None	None	None	None	N
E/S	0.1465	likely_benign	0.1436	benign	0.095	Stabilizing	0.983	D	0.531	neutral	None	None	None	None	N
E/T	0.1496	likely_benign	0.1479	benign	0.214	Stabilizing	0.992	D	0.557	neutral	None	None	None	None	N
E/V	0.1442	likely_benign	0.1425	benign	0.178	Stabilizing	0.999	D	0.569	neutral	N	0.487807257	None	None	N
E/W	0.7422	likely_pathogenic	0.7597	pathogenic	-0.013	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.467	ambiguous	0.4897	ambiguous	0.158	Stabilizing	0.999	D	0.652	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.