TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8852	26779;26780;26781	chr2:178714104;178714103;178714102	chr2:179578831;179578830;179578829
N2AB	8535	25828;25829;25830	chr2:178714104;178714103;178714102	chr2:179578831;179578830;179578829
N2A	7608	23047;23048;23049	chr2:178714104;178714103;178714102	chr2:179578831;179578830;179578829
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-74
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2232
• 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	rs777360482	None	None	N	0.345	0.12	0.29132392195	gnomAD-4.0.0	6.8426E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73491E-04	0	0	0
T/K	rs777360482	-0.575	None	N	0.207	0.132	0.254761474806	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
T/K	rs777360482	-0.575	None	N	0.207	0.132	0.254761474806	gnomAD-4.0.0	3.4213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47858E-05	3.31378E-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	0.0768	likely_benign	0.0761	benign	-0.964	Destabilizing	None	N	0.153	neutral	N	0.486633821	None	None	N
T/C	0.3688	ambiguous	0.4041	ambiguous	-0.78	Destabilizing	0.356	N	0.486	neutral	None	None	None	None	N
T/D	0.3805	ambiguous	0.4088	ambiguous	-0.633	Destabilizing	0.038	N	0.454	neutral	None	None	None	None	N
T/E	0.2409	likely_benign	0.255	benign	-0.585	Destabilizing	0.038	N	0.455	neutral	None	None	None	None	N
T/F	0.169	likely_benign	0.1846	benign	-0.86	Destabilizing	0.214	N	0.566	neutral	None	None	None	None	N
T/G	0.2519	likely_benign	0.2682	benign	-1.264	Destabilizing	0.016	N	0.451	neutral	None	None	None	None	N
T/H	0.2024	likely_benign	0.2147	benign	-1.482	Destabilizing	0.356	N	0.519	neutral	None	None	None	None	N
T/I	0.0902	likely_benign	0.1051	benign	-0.239	Destabilizing	None	N	0.345	neutral	N	0.490098201	None	None	N
T/K	0.1281	likely_benign	0.1243	benign	-0.826	Destabilizing	None	N	0.207	neutral	N	0.437839797	None	None	N
T/L	0.0693	likely_benign	0.0755	benign	-0.239	Destabilizing	0.002	N	0.357	neutral	None	None	None	None	N
T/M	0.0728	likely_benign	0.0834	benign	-0.061	Destabilizing	0.002	N	0.341	neutral	None	None	None	None	N
T/N	0.1265	likely_benign	0.1325	benign	-0.933	Destabilizing	0.038	N	0.379	neutral	None	None	None	None	N
T/P	0.2214	likely_benign	0.2335	benign	-0.449	Destabilizing	0.055	N	0.523	neutral	N	0.506259732	None	None	N
T/Q	0.172	likely_benign	0.186	benign	-1.056	Destabilizing	0.072	N	0.553	neutral	None	None	None	None	N
T/R	0.097	likely_benign	0.1011	benign	-0.645	Destabilizing	0.029	N	0.501	neutral	N	0.452790606	None	None	N
T/S	0.1061	likely_benign	0.1098	benign	-1.214	Destabilizing	None	N	0.153	neutral	N	0.462487525	None	None	N
T/V	0.0791	likely_benign	0.088	benign	-0.449	Destabilizing	None	N	0.152	neutral	None	None	None	None	N
T/W	0.4606	ambiguous	0.5207	ambiguous	-0.794	Destabilizing	0.864	D	0.544	neutral	None	None	None	None	N
T/Y	0.2213	likely_benign	0.2397	benign	-0.547	Destabilizing	0.356	N	0.545	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.