TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8667	26224;26225;26226	chr2:178715187;178715186;178715185	chr2:179579914;179579913;179579912
N2AB	8350	25273;25274;25275	chr2:178715187;178715186;178715185	chr2:179579914;179579913;179579912
N2A	7423	22492;22493;22494	chr2:178715187;178715186;178715185	chr2:179579914;179579913;179579912
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-72
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3108
• 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
Q/E	None	None	0.01	N	0.149	0.081	0.0986583533028	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02407E-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
Q/A	0.1671	likely_benign	0.1453	benign	-0.416	Destabilizing	0.001	N	0.092	neutral	None	None	None	None	N
Q/C	0.4133	ambiguous	0.4093	ambiguous	-0.012	Destabilizing	0.708	D	0.339	neutral	None	None	None	None	N
Q/D	0.306	likely_benign	0.2878	benign	0.229	Stabilizing	0.044	N	0.19	neutral	None	None	None	None	N
Q/E	0.0789	likely_benign	0.0763	benign	0.281	Stabilizing	0.01	N	0.149	neutral	N	0.430737679	None	None	N
Q/F	0.4165	ambiguous	0.4035	ambiguous	-0.324	Destabilizing	0.597	D	0.423	neutral	None	None	None	None	N
Q/G	0.232	likely_benign	0.2025	benign	-0.692	Destabilizing	0.033	N	0.218	neutral	None	None	None	None	N
Q/H	0.1282	likely_benign	0.1229	benign	-0.32	Destabilizing	0.444	N	0.25	neutral	N	0.498869613	None	None	N
Q/I	0.2346	likely_benign	0.2414	benign	0.252	Stabilizing	0.232	N	0.397	neutral	None	None	None	None	N
Q/K	0.0855	likely_benign	0.0846	benign	0.025	Stabilizing	None	N	0.057	neutral	N	0.439050518	None	None	N
Q/L	0.085	likely_benign	0.0861	benign	0.252	Stabilizing	0.044	N	0.255	neutral	N	0.487652541	None	None	N
Q/M	0.2588	likely_benign	0.2607	benign	0.355	Stabilizing	0.763	D	0.259	neutral	None	None	None	None	N
Q/N	0.2515	likely_benign	0.2488	benign	-0.507	Destabilizing	0.044	N	0.2	neutral	None	None	None	None	N
Q/P	0.6476	likely_pathogenic	0.5642	pathogenic	0.059	Stabilizing	0.146	N	0.306	neutral	D	0.522477191	None	None	N
Q/R	0.082	likely_benign	0.0797	benign	0.15	Stabilizing	None	N	0.089	neutral	N	0.450961023	None	None	N
Q/S	0.1792	likely_benign	0.1651	benign	-0.598	Destabilizing	0.001	N	0.06	neutral	None	None	None	None	N
Q/T	0.1467	likely_benign	0.1378	benign	-0.355	Destabilizing	0.001	N	0.285	neutral	None	None	None	None	N
Q/V	0.1719	likely_benign	0.1733	benign	0.059	Stabilizing	0.018	N	0.259	neutral	None	None	None	None	N
Q/W	0.2793	likely_benign	0.2676	benign	-0.226	Destabilizing	0.978	D	0.302	neutral	None	None	None	None	N
Q/Y	0.2662	likely_benign	0.2604	benign	0.012	Stabilizing	0.818	D	0.356	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.