TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17483	52672;52673;52674	chr2:178608436;178608435;178608434	chr2:179473163;179473162;179473161
N2AB	15842	47749;47750;47751	chr2:178608436;178608435;178608434	chr2:179473163;179473162;179473161
N2A	14915	44968;44969;44970	chr2:178608436;178608435;178608434	chr2:179473163;179473162;179473161
N2B	8418	25477;25478;25479	chr2:178608436;178608435;178608434	chr2:179473163;179473162;179473161
Novex-1	8543	25852;25853;25854	chr2:178608436;178608435;178608434	chr2:179473163;179473162;179473161
Novex-2	8610	26053;26054;26055	chr2:178608436;178608435;178608434	chr2:179473163;179473162;179473161
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: Fn3-15
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2416
• 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/A	None	None	0.76	N	0.491	0.318	0.191931220699	gnomAD-4.0.0	1.60622E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42365E-04	0	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	0.2177	likely_benign	0.1773	benign	-0.528	Destabilizing	0.76	D	0.491	neutral	N	0.471501051	None	None	N
T/C	0.6252	likely_pathogenic	0.4567	ambiguous	-0.526	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
T/D	0.5503	ambiguous	0.5033	ambiguous	-1.56	Destabilizing	0.986	D	0.475	neutral	None	None	None	None	N
T/E	0.6449	likely_pathogenic	0.618	pathogenic	-1.535	Destabilizing	0.986	D	0.469	neutral	None	None	None	None	N
T/F	0.5772	likely_pathogenic	0.4924	ambiguous	-0.816	Destabilizing	0.986	D	0.581	neutral	None	None	None	None	N
T/G	0.3202	likely_benign	0.2485	benign	-0.787	Destabilizing	0.91	D	0.493	neutral	None	None	None	None	N
T/H	0.4103	ambiguous	0.3565	ambiguous	-1.296	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
T/I	0.698	likely_pathogenic	0.6537	pathogenic	0.074	Stabilizing	0.964	D	0.475	neutral	N	0.505356158	None	None	N
T/K	0.28	likely_benign	0.3067	benign	-0.766	Destabilizing	0.986	D	0.479	neutral	None	None	None	None	N
T/L	0.3036	likely_benign	0.2454	benign	0.074	Stabilizing	0.91	D	0.429	neutral	None	None	None	None	N
T/M	0.2477	likely_benign	0.1998	benign	0.537	Stabilizing	0.807	D	0.373	neutral	None	None	None	None	N
T/N	0.1719	likely_benign	0.1506	benign	-1.095	Destabilizing	0.982	D	0.519	neutral	N	0.50534172	None	None	N
T/P	0.8284	likely_pathogenic	0.8185	pathogenic	-0.095	Destabilizing	0.991	D	0.523	neutral	N	0.501735307	None	None	N
T/Q	0.3546	ambiguous	0.3414	ambiguous	-1.297	Destabilizing	0.993	D	0.527	neutral	None	None	None	None	N
T/R	0.2508	likely_benign	0.2593	benign	-0.532	Destabilizing	0.986	D	0.519	neutral	None	None	None	None	N
T/S	0.1307	likely_benign	0.1059	benign	-1.097	Destabilizing	0.17	N	0.303	neutral	N	0.461377512	None	None	N
T/V	0.5107	ambiguous	0.4582	ambiguous	-0.095	Destabilizing	0.91	D	0.455	neutral	None	None	None	None	N
T/W	0.8833	likely_pathogenic	0.8202	pathogenic	-0.93	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
T/Y	0.5936	likely_pathogenic	0.4794	ambiguous	-0.565	Destabilizing	0.998	D	0.593	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.