TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7012	21259;21260;21261	chr2:178724341;178724340;178724339	chr2:179589068;179589067;179589066
N2AB	6695	20308;20309;20310	chr2:178724341;178724340;178724339	chr2:179589068;179589067;179589066
N2A	5768	17527;17528;17529	chr2:178724341;178724340;178724339	chr2:179589068;179589067;179589066
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: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-54
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.9092
• 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/S	rs1024577519	0.021	0.012	N	0.298	0.067	0.0846915920261	gnomAD-2.1.1	2.14E-05	None	None	None	None	I	None	2.48057E-04	0	None	0	0	None	0	None	0	0	0
R/S	rs1024577519	0.021	0.012	N	0.298	0.067	0.0846915920261	gnomAD-3.1.2	5.92E-05	None	None	None	None	I	None	2.17108E-04	0	0	0	0	None	0	0	0	0	0
R/S	rs1024577519	0.021	0.012	N	0.298	0.067	0.0846915920261	gnomAD-4.0.0	1.85937E-05	None	None	None	None	I	None	3.33796E-04	3.33589E-05	None	0	0	None	0	0	0	0	4.80461E-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	0.1693	likely_benign	0.1301	benign	0.106	Stabilizing	0.007	N	0.283	neutral	None	None	None	None	I
R/C	0.1963	likely_benign	0.1937	benign	-0.216	Destabilizing	0.864	D	0.24	neutral	None	None	None	None	I
R/D	0.364	ambiguous	0.2734	benign	-0.245	Destabilizing	0.031	N	0.317	neutral	None	None	None	None	I
R/E	0.1838	likely_benign	0.1327	benign	-0.18	Destabilizing	0.007	N	0.259	neutral	None	None	None	None	I
R/F	0.3443	ambiguous	0.283	benign	-0.128	Destabilizing	0.214	N	0.349	neutral	None	None	None	None	I
R/G	0.1169	likely_benign	0.0919	benign	-0.072	Destabilizing	0.024	N	0.309	neutral	N	0.493862785	None	None	I
R/H	0.1026	likely_benign	0.1006	benign	-0.591	Destabilizing	0.214	N	0.317	neutral	None	None	None	None	I
R/I	0.1405	likely_benign	0.1206	benign	0.535	Stabilizing	None	N	0.305	neutral	None	None	None	None	I
R/K	0.0674	likely_benign	0.0591	benign	-0.08	Destabilizing	None	N	0.171	neutral	N	0.37270723	None	None	I
R/L	0.1238	likely_benign	0.1037	benign	0.535	Stabilizing	0.016	N	0.277	neutral	None	None	None	None	I
R/M	0.1281	likely_benign	0.1026	benign	-0.031	Destabilizing	0.171	N	0.305	neutral	N	0.467926977	None	None	I
R/N	0.2582	likely_benign	0.1903	benign	-0.026	Destabilizing	0.072	N	0.321	neutral	None	None	None	None	I
R/P	0.1501	likely_benign	0.1225	benign	0.412	Stabilizing	None	N	0.231	neutral	None	None	None	None	I
R/Q	0.0802	likely_benign	0.0726	benign	-0.04	Destabilizing	None	N	0.169	neutral	None	None	None	None	I
R/S	0.2014	likely_benign	0.1543	benign	-0.223	Destabilizing	0.012	N	0.298	neutral	N	0.44208717	None	None	I
R/T	0.1202	likely_benign	0.0994	benign	-0.032	Destabilizing	0.024	N	0.342	neutral	N	0.453130883	None	None	I
R/V	0.1964	likely_benign	0.1562	benign	0.412	Stabilizing	0.016	N	0.283	neutral	None	None	None	None	I
R/W	0.1364	likely_benign	0.1249	benign	-0.278	Destabilizing	0.828	D	0.247	neutral	N	0.485320659	None	None	I
R/Y	0.2579	likely_benign	0.207	benign	0.137	Stabilizing	0.356	N	0.379	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.