TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8790	26593;26594;26595	chr2:178714406;178714405;178714404	chr2:179579133;179579132;179579131
N2AB	8473	25642;25643;25644	chr2:178714406;178714405;178714404	chr2:179579133;179579132;179579131
N2A	7546	22861;22862;22863	chr2:178714406;178714405;178714404	chr2:179579133;179579132;179579131
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-73
• Domain position: 55
• Structural Position: 134
• Q(SASA): 0.5289
• 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
N/D	rs772728050	0.276	0.048	D	0.394	0.173	0.211220785272	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	0	None	0	3.07377E-04	None	0	None	0	0	0
N/D	rs772728050	0.276	0.048	D	0.394	0.173	0.211220785272	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92604E-04	None	0	0	0	0	0
N/D	rs772728050	0.276	0.048	D	0.394	0.173	0.211220785272	gnomAD-4.0.0	2.47876E-06	None	None	None	None	N	None	0	0	None	0	8.91107E-05	None	0	0	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
N/A	0.2562	likely_benign	0.3288	benign	-0.744	Destabilizing	0.011	N	0.442	neutral	None	None	None	None	N
N/C	0.3873	ambiguous	0.4659	ambiguous	0.105	Stabilizing	0.863	D	0.571	neutral	None	None	None	None	N
N/D	0.1199	likely_benign	0.14	benign	0.162	Stabilizing	0.048	N	0.394	neutral	D	0.528093655	None	None	N
N/E	0.2814	likely_benign	0.3424	ambiguous	0.234	Stabilizing	0.101	N	0.355	neutral	None	None	None	None	N
N/F	0.544	ambiguous	0.6457	pathogenic	-0.582	Destabilizing	0.746	D	0.56	neutral	None	None	None	None	N
N/G	0.2268	likely_benign	0.2525	benign	-1.052	Destabilizing	0.104	N	0.315	neutral	None	None	None	None	N
N/H	0.1015	likely_benign	0.1141	benign	-0.719	Destabilizing	0.002	N	0.212	neutral	N	0.498672158	None	None	N
N/I	0.3296	likely_benign	0.4497	ambiguous	0.023	Stabilizing	0.454	N	0.562	neutral	N	0.498925647	None	None	N
N/K	0.1551	likely_benign	0.1921	benign	-0.024	Destabilizing	0.002	N	0.199	neutral	N	0.491693491	None	None	N
N/L	0.3311	likely_benign	0.4171	ambiguous	0.023	Stabilizing	0.239	N	0.52	neutral	None	None	None	None	N
N/M	0.3304	likely_benign	0.401	ambiguous	0.298	Stabilizing	0.962	D	0.543	neutral	None	None	None	None	N
N/P	0.6442	likely_pathogenic	0.7452	pathogenic	-0.203	Destabilizing	0.191	N	0.549	neutral	None	None	None	None	N
N/Q	0.2251	likely_benign	0.2606	benign	-0.509	Destabilizing	0.524	D	0.44	neutral	None	None	None	None	N
N/R	0.2103	likely_benign	0.2547	benign	-0.048	Destabilizing	0.296	N	0.411	neutral	None	None	None	None	N
N/S	0.1174	likely_benign	0.1334	benign	-0.611	Destabilizing	None	N	0.137	neutral	N	0.484869862	None	None	N
N/T	0.1671	likely_benign	0.2059	benign	-0.344	Destabilizing	0.038	N	0.363	neutral	N	0.494784591	None	None	N
N/V	0.3619	ambiguous	0.4731	ambiguous	-0.203	Destabilizing	0.084	N	0.529	neutral	None	None	None	None	N
N/W	0.7087	likely_pathogenic	0.7801	pathogenic	-0.351	Destabilizing	0.986	D	0.601	neutral	None	None	None	None	N
N/Y	0.1522	likely_benign	0.1932	benign	-0.147	Destabilizing	0.526	D	0.553	neutral	N	0.518422254	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.