TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6582	19969;19970;19971	chr2:178727834;178727833;178727832	chr2:179592561;179592560;179592559
N2AB	6265	19018;19019;19020	chr2:178727834;178727833;178727832	chr2:179592561;179592560;179592559
N2A	5338	16237;16238;16239	chr2:178727834;178727833;178727832	chr2:179592561;179592560;179592559
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: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Ig-50
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5605
• 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
R/Q	rs776051087	-0.096	0.953	N	0.336	0.213	None	gnomAD-2.1.1	2.96E-05	None	None	None	None	I	None	8.35E-05	3E-05	None	0	0	None	7.17E-05	None	0	1.6E-05	1.46071E-04
R/Q	rs776051087	-0.096	0.953	N	0.336	0.213	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	I	None	1.20755E-04	0	0	0	0	None	0	0	4.41E-05	0	4.78469E-04
R/Q	rs776051087	-0.096	0.953	N	0.336	0.213	None	gnomAD-4.0.0	2.81502E-05	None	None	None	None	I	None	1.07637E-04	1.71727E-05	None	3.44187E-05	0	None	1.57015E-05	0	1.96177E-05	1.0281E-04	3.23771E-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
R/A	0.1976	likely_benign	0.1983	benign	0.114	Stabilizing	0.176	N	0.269	neutral	None	None	None	None	I
R/C	0.144	likely_benign	0.1426	benign	-0.065	Destabilizing	0.995	D	0.293	neutral	None	None	None	None	I
R/D	0.3079	likely_benign	0.3094	benign	-0.199	Destabilizing	0.543	D	0.335	neutral	None	None	None	None	I
R/E	0.1662	likely_benign	0.1646	benign	-0.151	Destabilizing	0.495	N	0.256	neutral	None	None	None	None	I
R/F	0.3048	likely_benign	0.3318	benign	-0.149	Destabilizing	0.981	D	0.32	neutral	None	None	None	None	I
R/G	0.1261	likely_benign	0.1214	benign	-0.047	Destabilizing	0.485	N	0.285	neutral	N	0.372571157	None	None	I
R/H	0.0791	likely_benign	0.0805	benign	-0.553	Destabilizing	0.944	D	0.348	neutral	None	None	None	None	I
R/I	0.1309	likely_benign	0.1355	benign	0.497	Stabilizing	0.944	D	0.379	neutral	None	None	None	None	I
R/K	0.0868	likely_benign	0.0894	benign	0.015	Stabilizing	0.495	N	0.286	neutral	None	None	None	None	I
R/L	0.1349	likely_benign	0.1407	benign	0.497	Stabilizing	0.82	D	0.331	neutral	N	0.456861835	None	None	I
R/M	0.1477	likely_benign	0.1489	benign	0.046	Stabilizing	0.981	D	0.329	neutral	None	None	None	None	I
R/N	0.2595	likely_benign	0.2569	benign	0.183	Stabilizing	0.031	N	0.112	neutral	None	None	None	None	I
R/P	0.1781	likely_benign	0.1855	benign	0.389	Stabilizing	0.014	N	0.195	neutral	N	0.339997379	None	None	I
R/Q	0.075	likely_benign	0.0756	benign	0.114	Stabilizing	0.953	D	0.336	neutral	N	0.432523538	None	None	I
R/S	0.1946	likely_benign	0.1986	benign	-0.036	Destabilizing	0.004	N	0.132	neutral	None	None	None	None	I
R/T	0.1212	likely_benign	0.1192	benign	0.126	Stabilizing	0.329	N	0.271	neutral	None	None	None	None	I
R/V	0.1981	likely_benign	0.202	benign	0.389	Stabilizing	0.704	D	0.413	neutral	None	None	None	None	I
R/W	0.1186	likely_benign	0.1405	benign	-0.295	Destabilizing	0.995	D	0.364	neutral	None	None	None	None	I
R/Y	0.2159	likely_benign	0.2373	benign	0.116	Stabilizing	0.981	D	0.317	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.