TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17895	53908;53909;53910	chr2:178605612;178605611;178605610	chr2:179470339;179470338;179470337
N2AB	16254	48985;48986;48987	chr2:178605612;178605611;178605610	chr2:179470339;179470338;179470337
N2A	15327	46204;46205;46206	chr2:178605612;178605611;178605610	chr2:179470339;179470338;179470337
N2B	8830	26713;26714;26715	chr2:178605612;178605611;178605610	chr2:179470339;179470338;179470337
Novex-1	8955	27088;27089;27090	chr2:178605612;178605611;178605610	chr2:179470339;179470338;179470337
Novex-2	9022	27289;27290;27291	chr2:178605612;178605611;178605610	chr2:179470339;179470338;179470337
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-18
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4483
• Predicted PPI site: I

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	rs796463261	None	0.025	N	0.202	0.085	0.15556083564	gnomAD-3.1.2	6.61E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/E	rs796463261	None	0.025	N	0.202	0.085	0.15556083564	gnomAD-4.0.0	1.32022E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.94863E-05	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
Q/A	0.1539	likely_benign	0.1301	benign	-0.28	Destabilizing	0.015	N	0.177	neutral	None	None	None	None	I
Q/C	0.4057	ambiguous	0.3476	ambiguous	0.107	Stabilizing	0.781	D	0.279	neutral	None	None	None	None	I
Q/D	0.4204	ambiguous	0.3328	benign	0.095	Stabilizing	0.064	N	0.227	neutral	None	None	None	None	I
Q/E	0.0925	likely_benign	0.0853	benign	0.109	Stabilizing	0.025	N	0.202	neutral	N	0.442596963	None	None	I
Q/F	0.4835	ambiguous	0.3949	ambiguous	-0.284	Destabilizing	0.142	N	0.423	neutral	None	None	None	None	I
Q/G	0.3141	likely_benign	0.2342	benign	-0.524	Destabilizing	0.064	N	0.251	neutral	None	None	None	None	I
Q/H	0.1656	likely_benign	0.1294	benign	-0.281	Destabilizing	0.47	N	0.267	neutral	N	0.497490241	None	None	I
Q/I	0.1638	likely_benign	0.1362	benign	0.287	Stabilizing	None	N	0.143	neutral	None	None	None	None	I
Q/K	0.0722	likely_benign	0.0626	benign	-0.046	Destabilizing	None	N	0.077	neutral	N	0.43846058	None	None	I
Q/L	0.0656	likely_benign	0.0549	benign	0.287	Stabilizing	None	N	0.113	neutral	N	0.414332927	None	None	I
Q/M	0.2029	likely_benign	0.177	benign	0.412	Stabilizing	0.367	N	0.299	neutral	None	None	None	None	I
Q/N	0.2613	likely_benign	0.1991	benign	-0.395	Destabilizing	0.142	N	0.239	neutral	None	None	None	None	I
Q/P	0.6601	likely_pathogenic	0.4455	ambiguous	0.128	Stabilizing	0.202	N	0.358	neutral	N	0.472293837	None	None	I
Q/R	0.0819	likely_benign	0.0705	benign	0.11	Stabilizing	0.025	N	0.235	neutral	N	0.427224866	None	None	I
Q/S	0.189	likely_benign	0.1462	benign	-0.437	Destabilizing	0.015	N	0.177	neutral	None	None	None	None	I
Q/T	0.1059	likely_benign	0.0884	benign	-0.255	Destabilizing	0.001	N	0.118	neutral	None	None	None	None	I
Q/V	0.1228	likely_benign	0.1074	benign	0.128	Stabilizing	0.006	N	0.19	neutral	None	None	None	None	I
Q/W	0.45	ambiguous	0.3624	ambiguous	-0.241	Destabilizing	0.931	D	0.252	neutral	None	None	None	None	I
Q/Y	0.3541	ambiguous	0.2881	benign	-0.007	Destabilizing	0.251	N	0.373	neutral	None	None	None	None	I

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.