TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32222	96889;96890;96891	chr2:178543309;178543308;178543307	chr2:179408036;179408035;179408034
N2AB	30581	91966;91967;91968	chr2:178543309;178543308;178543307	chr2:179408036;179408035;179408034
N2A	29654	89185;89186;89187	chr2:178543309;178543308;178543307	chr2:179408036;179408035;179408034
N2B	23157	69694;69695;69696	chr2:178543309;178543308;178543307	chr2:179408036;179408035;179408034
Novex-1	23282	70069;70070;70071	chr2:178543309;178543308;178543307	chr2:179408036;179408035;179408034
Novex-2	23349	70270;70271;70272	chr2:178543309;178543308;178543307	chr2:179408036;179408035;179408034
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-123
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1616
• 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
A/P	None	None	0.996	N	0.542	0.342	0.482936932564	gnomAD-4.0.0	6.84179E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	0	0	0
A/T	None	None	0.959	N	0.467	0.266	0.339793275041	gnomAD-4.0.0	6.84179E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6564E-05

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
A/C	0.3419	ambiguous	0.3277	benign	-0.811	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
A/D	0.4515	ambiguous	0.4238	ambiguous	-2.255	Highly Destabilizing	0.959	D	0.535	neutral	N	0.502357343	None	None	N
A/E	0.294	likely_benign	0.2875	benign	-2.043	Highly Destabilizing	0.884	D	0.472	neutral	None	None	None	None	N
A/F	0.2822	likely_benign	0.2603	benign	-0.514	Destabilizing	0.991	D	0.618	neutral	None	None	None	None	N
A/G	0.1196	likely_benign	0.1166	benign	-1.347	Destabilizing	0.035	N	0.197	neutral	N	0.465185822	None	None	N
A/H	0.3557	ambiguous	0.3531	ambiguous	-1.977	Destabilizing	0.1	N	0.515	neutral	None	None	None	None	N
A/I	0.2165	likely_benign	0.1998	benign	0.43	Stabilizing	0.997	D	0.541	neutral	None	None	None	None	N
A/K	0.2865	likely_benign	0.2986	benign	-1.083	Destabilizing	0.884	D	0.471	neutral	None	None	None	None	N
A/L	0.1475	likely_benign	0.1371	benign	0.43	Stabilizing	0.969	D	0.481	neutral	None	None	None	None	N
A/M	0.196	likely_benign	0.1825	benign	0.174	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
A/N	0.2756	likely_benign	0.2605	benign	-1.39	Destabilizing	0.939	D	0.535	neutral	None	None	None	None	N
A/P	0.9142	likely_pathogenic	0.8976	pathogenic	0.042	Stabilizing	0.996	D	0.542	neutral	N	0.48710641	None	None	N
A/Q	0.2386	likely_benign	0.2428	benign	-1.158	Destabilizing	0.579	D	0.391	neutral	None	None	None	None	N
A/R	0.2221	likely_benign	0.2307	benign	-1.248	Destabilizing	0.046	N	0.411	neutral	None	None	None	None	N
A/S	0.0896	likely_benign	0.0878	benign	-1.748	Destabilizing	0.826	D	0.447	neutral	N	0.39984069	None	None	N
A/T	0.0847	likely_benign	0.0804	benign	-1.416	Destabilizing	0.959	D	0.467	neutral	N	0.39549645	None	None	N
A/V	0.1245	likely_benign	0.1172	benign	0.042	Stabilizing	0.959	D	0.485	neutral	N	0.478096404	None	None	N
A/W	0.6663	likely_pathogenic	0.644	pathogenic	-1.41	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
A/Y	0.3986	ambiguous	0.3845	ambiguous	-0.776	Destabilizing	0.982	D	0.588	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.