TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4976	15151;15152;15153	chr2:178735520;178735519;178735518	chr2:179600247;179600246;179600245
N2AB	4659	14200;14201;14202	chr2:178735520;178735519;178735518	chr2:179600247;179600246;179600245
N2A	3732	11419;11420;11421	chr2:178735520;178735519;178735518	chr2:179600247;179600246;179600245
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-32
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3568
• 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	None	None	0.188	N	0.398	0.254	0.0884992946249	gnomAD-4.0.0	7.01756E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.11057E-07	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	0.074	likely_benign	0.0797	benign	-0.713	Destabilizing	None	N	0.142	neutral	N	0.50517243	None	None	N
T/C	0.3598	ambiguous	0.3992	ambiguous	-0.429	Destabilizing	0.824	D	0.417	neutral	None	None	None	None	N
T/D	0.2685	likely_benign	0.3265	benign	0.003	Stabilizing	0.081	N	0.395	neutral	None	None	None	None	N
T/E	0.232	likely_benign	0.2762	benign	-0.046	Destabilizing	0.002	N	0.281	neutral	None	None	None	None	N
T/F	0.1484	likely_benign	0.1654	benign	-1.053	Destabilizing	0.38	N	0.527	neutral	None	None	None	None	N
T/G	0.22	likely_benign	0.2702	benign	-0.889	Destabilizing	0.081	N	0.497	neutral	None	None	None	None	N
T/H	0.1979	likely_benign	0.22	benign	-1.262	Destabilizing	0.824	D	0.501	neutral	None	None	None	None	N
T/I	0.1032	likely_benign	0.1185	benign	-0.353	Destabilizing	0.188	N	0.398	neutral	N	0.474099539	None	None	N
T/K	0.1958	likely_benign	0.2184	benign	-0.483	Destabilizing	0.002	N	0.281	neutral	None	None	None	None	N
T/L	0.0798	likely_benign	0.0895	benign	-0.353	Destabilizing	0.035	N	0.415	neutral	None	None	None	None	N
T/M	0.0771	likely_benign	0.0779	benign	0.025	Stabilizing	0.035	N	0.446	neutral	None	None	None	None	N
T/N	0.0995	likely_benign	0.1133	benign	-0.289	Destabilizing	0.062	N	0.375	neutral	N	0.510384599	None	None	N
T/P	0.3059	likely_benign	0.3735	ambiguous	-0.444	Destabilizing	0.317	N	0.409	neutral	D	0.655242522	None	None	N
T/Q	0.2045	likely_benign	0.2242	benign	-0.59	Destabilizing	0.38	N	0.404	neutral	None	None	None	None	N
T/R	0.1541	likely_benign	0.1639	benign	-0.226	Destabilizing	0.081	N	0.409	neutral	None	None	None	None	N
T/S	0.0906	likely_benign	0.0984	benign	-0.586	Destabilizing	None	N	0.247	neutral	N	0.50371934	None	None	N
T/V	0.1	likely_benign	0.1142	benign	-0.444	Destabilizing	0.081	N	0.344	neutral	None	None	None	None	N
T/W	0.436	ambiguous	0.4819	ambiguous	-0.944	Destabilizing	0.935	D	0.567	neutral	None	None	None	None	N
T/Y	0.1987	likely_benign	0.2277	benign	-0.698	Destabilizing	0.555	D	0.523	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.