TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32485	97678;97679;97680	chr2:178542303;178542302;178542301	chr2:179407030;179407029;179407028
N2AB	30844	92755;92756;92757	chr2:178542303;178542302;178542301	chr2:179407030;179407029;179407028
N2A	29917	89974;89975;89976	chr2:178542303;178542302;178542301	chr2:179407030;179407029;179407028
N2B	23420	70483;70484;70485	chr2:178542303;178542302;178542301	chr2:179407030;179407029;179407028
Novex-1	23545	70858;70859;70860	chr2:178542303;178542302;178542301	chr2:179407030;179407029;179407028
Novex-2	23612	71059;71060;71061	chr2:178542303;178542302;178542301	chr2:179407030;179407029;179407028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-124
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.7609
• 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
Y/H	None	None	0.998	N	0.673	0.324	0.324161360171	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
Y/A	0.7464	likely_pathogenic	0.6284	pathogenic	-2.469	Highly Destabilizing	0.985	D	0.588	neutral	None	None	None	None	I
Y/C	0.3106	likely_benign	0.2179	benign	-1.094	Destabilizing	1.0	D	0.719	prob.delet.	N	0.472199753	None	None	I
Y/D	0.8293	likely_pathogenic	0.769	pathogenic	-2.285	Highly Destabilizing	0.998	D	0.705	prob.neutral	N	0.471946264	None	None	I
Y/E	0.9492	likely_pathogenic	0.9262	pathogenic	-2.103	Highly Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
Y/F	0.0948	likely_benign	0.0875	benign	-0.747	Destabilizing	0.031	N	0.194	neutral	N	0.429251159	None	None	I
Y/G	0.7006	likely_pathogenic	0.5897	pathogenic	-2.86	Highly Destabilizing	0.999	D	0.604	neutral	None	None	None	None	I
Y/H	0.466	ambiguous	0.3715	ambiguous	-1.362	Destabilizing	0.998	D	0.673	neutral	N	0.460589958	None	None	I
Y/I	0.8358	likely_pathogenic	0.7807	pathogenic	-1.204	Destabilizing	0.97	D	0.63	neutral	None	None	None	None	I
Y/K	0.9568	likely_pathogenic	0.94	pathogenic	-1.424	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
Y/L	0.7952	likely_pathogenic	0.7392	pathogenic	-1.204	Destabilizing	0.871	D	0.627	neutral	None	None	None	None	I
Y/M	0.867	likely_pathogenic	0.8249	pathogenic	-0.898	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
Y/N	0.6011	likely_pathogenic	0.5058	ambiguous	-2.067	Highly Destabilizing	0.998	D	0.715	prob.delet.	N	0.460589958	None	None	I
Y/P	0.6505	likely_pathogenic	0.5385	ambiguous	-1.634	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
Y/Q	0.9124	likely_pathogenic	0.8548	pathogenic	-1.875	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
Y/R	0.9105	likely_pathogenic	0.867	pathogenic	-1.199	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
Y/S	0.489	ambiguous	0.3727	ambiguous	-2.506	Highly Destabilizing	0.998	D	0.615	neutral	N	0.470678816	None	None	I
Y/T	0.8085	likely_pathogenic	0.7365	pathogenic	-2.212	Highly Destabilizing	0.999	D	0.621	neutral	None	None	None	None	I
Y/V	0.7155	likely_pathogenic	0.6424	pathogenic	-1.634	Destabilizing	0.97	D	0.615	neutral	None	None	None	None	I
Y/W	0.5101	ambiguous	0.4449	ambiguous	-0.12	Destabilizing	0.999	D	0.657	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.