TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7852	23779;23780;23781	chr2:178720088;178720087;178720086	chr2:179584815;179584814;179584813
N2AB	7535	22828;22829;22830	chr2:178720088;178720087;178720086	chr2:179584815;179584814;179584813
N2A	6608	20047;20048;20049	chr2:178720088;178720087;178720086	chr2:179584815;179584814;179584813
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-63
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.2161
• 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	None	D	0.202	0.202	0.230578612272	gnomAD-4.0.0	2.05273E-06	None	None	None	None	N	None	0	0	None	0	2.51965E-05	None	0	0	8.99522E-07	1.15937E-05	0
T/I	rs1183659807	None	0.001	N	0.325	0.264	0.465633601861	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/I	rs1183659807	None	0.001	N	0.325	0.264	0.465633601861	gnomAD-4.0.0	3.71838E-06	None	None	None	None	N	None	0	1.66706E-05	None	0	0	None	0	0	4.23831E-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	0.0944	likely_benign	0.088	benign	-1.157	Destabilizing	None	N	0.202	neutral	D	0.534947843	None	None	N
T/C	0.4882	ambiguous	0.4198	ambiguous	-0.904	Destabilizing	0.846	D	0.53	neutral	None	None	None	None	N
T/D	0.6151	likely_pathogenic	0.5485	ambiguous	-1.775	Destabilizing	0.094	N	0.537	neutral	None	None	None	None	N
T/E	0.3909	ambiguous	0.3571	ambiguous	-1.569	Destabilizing	0.09	N	0.519	neutral	None	None	None	None	N
T/F	0.2414	likely_benign	0.2027	benign	-0.777	Destabilizing	0.72	D	0.577	neutral	None	None	None	None	N
T/G	0.381	ambiguous	0.3313	benign	-1.568	Destabilizing	0.198	N	0.521	neutral	None	None	None	None	N
T/H	0.3031	likely_benign	0.2582	benign	-1.711	Destabilizing	0.881	D	0.553	neutral	None	None	None	None	N
T/I	0.1519	likely_benign	0.1257	benign	-0.075	Destabilizing	0.001	N	0.325	neutral	N	0.504400285	None	None	N
T/K	0.2784	likely_benign	0.2465	benign	-0.625	Destabilizing	0.121	N	0.523	neutral	None	None	None	None	N
T/L	0.1111	likely_benign	0.0952	benign	-0.075	Destabilizing	0.019	N	0.461	neutral	None	None	None	None	N
T/M	0.102	likely_benign	0.0964	benign	-0.166	Destabilizing	0.491	N	0.551	neutral	None	None	None	None	N
T/N	0.219	likely_benign	0.1882	benign	-1.343	Destabilizing	0.072	N	0.546	neutral	N	0.502323143	None	None	N
T/P	0.8569	likely_pathogenic	0.8167	pathogenic	-0.405	Destabilizing	0.135	N	0.548	neutral	D	0.533860845	None	None	N
T/Q	0.2819	likely_benign	0.2552	benign	-1.095	Destabilizing	0.311	N	0.559	neutral	None	None	None	None	N
T/R	0.209	likely_benign	0.1824	benign	-0.852	Destabilizing	0.72	D	0.551	neutral	None	None	None	None	N
T/S	0.1338	likely_benign	0.1193	benign	-1.5	Destabilizing	None	N	0.405	neutral	N	0.474051313	None	None	N
T/V	0.1175	likely_benign	0.1024	benign	-0.405	Destabilizing	0.014	N	0.483	neutral	None	None	None	None	N
T/W	0.649	likely_pathogenic	0.6004	pathogenic	-1.003	Destabilizing	0.984	D	0.615	neutral	None	None	None	None	N
T/Y	0.3149	likely_benign	0.2706	benign	-0.6	Destabilizing	0.839	D	0.578	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.