TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31968	96127;96128;96129	chr2:178544327;178544326;178544325	chr2:179409054;179409053;179409052
N2AB	30327	91204;91205;91206	chr2:178544327;178544326;178544325	chr2:179409054;179409053;179409052
N2A	29400	88423;88424;88425	chr2:178544327;178544326;178544325	chr2:179409054;179409053;179409052
N2B	22903	68932;68933;68934	chr2:178544327;178544326;178544325	chr2:179409054;179409053;179409052
Novex-1	23028	69307;69308;69309	chr2:178544327;178544326;178544325	chr2:179409054;179409053;179409052
Novex-2	23095	69508;69509;69510	chr2:178544327;178544326;178544325	chr2:179409054;179409053;179409052
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: Fn3-121
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.1857
• 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	0.029	N	0.462	0.199	0.165133752707	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85873E-06	0	0
T/N	rs1696025684	None	None	N	0.135	0.139	0.124217242631	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
T/N	rs1696025684	None	None	N	0.135	0.139	0.124217242631	gnomAD-4.0.0	2.56251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39338E-06	0	2.84495E-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
T/A	0.0773	likely_benign	0.0762	benign	-0.957	Destabilizing	None	N	0.131	neutral	N	0.496794101	None	None	N
T/C	0.17	likely_benign	0.1852	benign	-0.572	Destabilizing	0.356	N	0.501	neutral	None	None	None	None	N
T/D	0.3467	ambiguous	0.3433	ambiguous	-0.442	Destabilizing	0.016	N	0.397	neutral	None	None	None	None	N
T/E	0.333	likely_benign	0.3343	benign	-0.318	Destabilizing	0.016	N	0.398	neutral	None	None	None	None	N
T/F	0.3034	likely_benign	0.3133	benign	-0.79	Destabilizing	0.214	N	0.615	neutral	None	None	None	None	N
T/G	0.1749	likely_benign	0.1778	benign	-1.321	Destabilizing	0.007	N	0.366	neutral	None	None	None	None	N
T/H	0.2053	likely_benign	0.2134	benign	-1.384	Destabilizing	0.214	N	0.557	neutral	None	None	None	None	N
T/I	0.2075	likely_benign	0.2188	benign	-0.034	Destabilizing	0.029	N	0.462	neutral	N	0.501531043	None	None	N
T/K	0.1783	likely_benign	0.1887	benign	-0.471	Destabilizing	0.016	N	0.399	neutral	None	None	None	None	N
T/L	0.082	likely_benign	0.0828	benign	-0.034	Destabilizing	None	N	0.248	neutral	None	None	None	None	N
T/M	0.0881	likely_benign	0.0932	benign	-0.029	Destabilizing	0.214	N	0.503	neutral	None	None	None	None	N
T/N	0.0726	likely_benign	0.0727	benign	-0.842	Destabilizing	None	N	0.135	neutral	N	0.519289665	None	None	N
T/P	0.0957	likely_benign	0.0983	benign	-0.309	Destabilizing	None	N	0.251	neutral	N	0.508843385	None	None	N
T/Q	0.1969	likely_benign	0.2095	benign	-0.739	Destabilizing	0.072	N	0.523	neutral	None	None	None	None	N
T/R	0.1429	likely_benign	0.1543	benign	-0.481	Destabilizing	0.072	N	0.494	neutral	None	None	None	None	N
T/S	0.0996	likely_benign	0.1013	benign	-1.169	Destabilizing	None	N	0.172	neutral	N	0.477395946	None	None	N
T/V	0.147	likely_benign	0.1547	benign	-0.309	Destabilizing	0.016	N	0.284	neutral	None	None	None	None	N
T/W	0.5883	likely_pathogenic	0.6	pathogenic	-0.829	Destabilizing	0.864	D	0.603	neutral	None	None	None	None	N
T/Y	0.2467	likely_benign	0.2513	benign	-0.503	Destabilizing	0.356	N	0.603	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.