TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18331	55216;55217;55218	chr2:178602411;178602410;178602409	chr2:179467138;179467137;179467136
N2AB	16690	50293;50294;50295	chr2:178602411;178602410;178602409	chr2:179467138;179467137;179467136
N2A	15763	47512;47513;47514	chr2:178602411;178602410;178602409	chr2:179467138;179467137;179467136
N2B	9266	28021;28022;28023	chr2:178602411;178602410;178602409	chr2:179467138;179467137;179467136
Novex-1	9391	28396;28397;28398	chr2:178602411;178602410;178602409	chr2:179467138;179467137;179467136
Novex-2	9458	28597;28598;28599	chr2:178602411;178602410;178602409	chr2:179467138;179467137;179467136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-21
• Domain position: 60
• Structural Position: 88
• Q(SASA): 0.302
• 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
T/I	rs2053691447	None	0.497	N	0.675	0.254	0.499218193508	gnomAD-4.0.0	1.59343E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86207E-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
T/A	0.0711	likely_benign	0.0661	benign	-0.808	Destabilizing	None	N	0.19	neutral	N	0.473192016	None	None	N
T/C	0.396	ambiguous	0.3837	ambiguous	-0.54	Destabilizing	0.909	D	0.707	prob.neutral	None	None	None	None	N
T/D	0.2509	likely_benign	0.2372	benign	-0.086	Destabilizing	0.567	D	0.645	neutral	None	None	None	None	N
T/E	0.2341	likely_benign	0.2272	benign	-0.031	Destabilizing	0.157	N	0.618	neutral	None	None	None	None	N
T/F	0.2423	likely_benign	0.2402	benign	-0.927	Destabilizing	0.726	D	0.765	deleterious	None	None	None	None	N
T/G	0.161	likely_benign	0.1346	benign	-1.076	Destabilizing	0.157	N	0.606	neutral	None	None	None	None	N
T/H	0.2237	likely_benign	0.2144	benign	-1.093	Destabilizing	0.909	D	0.755	deleterious	None	None	None	None	N
T/I	0.2034	likely_benign	0.1967	benign	-0.172	Destabilizing	0.497	N	0.675	prob.neutral	N	0.492297852	None	None	N
T/K	0.1836	likely_benign	0.1745	benign	-0.46	Destabilizing	0.157	N	0.62	neutral	None	None	None	None	N
T/L	0.1231	likely_benign	0.1234	benign	-0.172	Destabilizing	0.157	N	0.575	neutral	None	None	None	None	N
T/M	0.122	likely_benign	0.122	benign	-0.259	Destabilizing	0.909	D	0.711	prob.delet.	None	None	None	None	N
T/N	0.1001	likely_benign	0.0968	benign	-0.615	Destabilizing	0.331	N	0.532	neutral	N	0.447370852	None	None	N
T/P	0.2112	likely_benign	0.2222	benign	-0.353	Destabilizing	0.497	N	0.703	prob.neutral	N	0.471764086	None	None	N
T/Q	0.2005	likely_benign	0.1923	benign	-0.603	Destabilizing	0.567	D	0.728	prob.delet.	None	None	None	None	N
T/R	0.1605	likely_benign	0.1582	benign	-0.295	Destabilizing	0.567	D	0.716	prob.delet.	None	None	None	None	N
T/S	0.0819	likely_benign	0.0753	benign	-0.911	Destabilizing	0.001	N	0.191	neutral	N	0.416029225	None	None	N
T/V	0.1424	likely_benign	0.137	benign	-0.353	Destabilizing	0.157	N	0.455	neutral	None	None	None	None	N
T/W	0.6175	likely_pathogenic	0.5935	pathogenic	-0.968	Destabilizing	0.968	D	0.741	deleterious	None	None	None	None	N
T/Y	0.2749	likely_benign	0.2688	benign	-0.662	Destabilizing	0.726	D	0.765	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.