TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23775	71548;71549;71550	chr2:178574809;178574808;178574807	chr2:179439536;179439535;179439534
N2AB	22134	66625;66626;66627	chr2:178574809;178574808;178574807	chr2:179439536;179439535;179439534
N2A	21207	63844;63845;63846	chr2:178574809;178574808;178574807	chr2:179439536;179439535;179439534
N2B	14710	44353;44354;44355	chr2:178574809;178574808;178574807	chr2:179439536;179439535;179439534
Novex-1	14835	44728;44729;44730	chr2:178574809;178574808;178574807	chr2:179439536;179439535;179439534
Novex-2	14902	44929;44930;44931	chr2:178574809;178574808;178574807	chr2:179439536;179439535;179439534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-60
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.457
• 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
V/L	rs377491708	-0.219	0.041	N	0.187	0.035	None	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	1.8E-05	0
V/L	rs377491708	-0.219	0.041	N	0.187	0.035	None	gnomAD-4.0.0	1.09579E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.44018E-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
V/A	0.1096	likely_benign	0.0932	benign	-1.049	Destabilizing	0.001	N	0.118	neutral	N	0.50083719	None	None	I
V/C	0.5318	ambiguous	0.4928	ambiguous	-0.67	Destabilizing	0.944	D	0.353	neutral	None	None	None	None	I
V/D	0.3359	likely_benign	0.2805	benign	-0.719	Destabilizing	0.627	D	0.372	neutral	N	0.513113054	None	None	I
V/E	0.2193	likely_benign	0.1986	benign	-0.763	Destabilizing	0.388	N	0.332	neutral	None	None	None	None	I
V/F	0.1532	likely_benign	0.1424	benign	-0.871	Destabilizing	0.627	D	0.39	neutral	N	0.467445219	None	None	I
V/G	0.1803	likely_benign	0.1617	benign	-1.299	Destabilizing	0.193	N	0.295	neutral	N	0.475687652	None	None	I
V/H	0.333	likely_benign	0.3069	benign	-0.743	Destabilizing	0.981	D	0.366	neutral	None	None	None	None	I
V/I	0.0705	likely_benign	0.0666	benign	-0.493	Destabilizing	0.006	N	0.165	neutral	N	0.483406223	None	None	I
V/K	0.218	likely_benign	0.2189	benign	-0.893	Destabilizing	0.388	N	0.31	neutral	None	None	None	None	I
V/L	0.1279	likely_benign	0.122	benign	-0.493	Destabilizing	0.041	N	0.187	neutral	N	0.466801975	None	None	I
V/M	0.0858	likely_benign	0.0769	benign	-0.41	Destabilizing	0.054	N	0.187	neutral	None	None	None	None	I
V/N	0.1416	likely_benign	0.1212	benign	-0.628	Destabilizing	0.69	D	0.389	neutral	None	None	None	None	I
V/P	0.8837	likely_pathogenic	0.8667	pathogenic	-0.643	Destabilizing	0.818	D	0.361	neutral	None	None	None	None	I
V/Q	0.1753	likely_benign	0.1673	benign	-0.827	Destabilizing	0.818	D	0.369	neutral	None	None	None	None	I
V/R	0.2202	likely_benign	0.2308	benign	-0.33	Destabilizing	0.69	D	0.39	neutral	None	None	None	None	I
V/S	0.1226	likely_benign	0.1066	benign	-1.089	Destabilizing	0.241	N	0.287	neutral	None	None	None	None	I
V/T	0.0906	likely_benign	0.0805	benign	-1.028	Destabilizing	0.001	N	0.103	neutral	None	None	None	None	I
V/W	0.7131	likely_pathogenic	0.6639	pathogenic	-1.007	Destabilizing	0.981	D	0.41	neutral	None	None	None	None	I
V/Y	0.4011	ambiguous	0.3516	ambiguous	-0.723	Destabilizing	0.818	D	0.385	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.