TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16871	50836;50837;50838	chr2:178611618;178611617;178611616	chr2:179476345;179476344;179476343
N2AB	15230	45913;45914;45915	chr2:178611618;178611617;178611616	chr2:179476345;179476344;179476343
N2A	14303	43132;43133;43134	chr2:178611618;178611617;178611616	chr2:179476345;179476344;179476343
N2B	7806	23641;23642;23643	chr2:178611618;178611617;178611616	chr2:179476345;179476344;179476343
Novex-1	7931	24016;24017;24018	chr2:178611618;178611617;178611616	chr2:179476345;179476344;179476343
Novex-2	7998	24217;24218;24219	chr2:178611618;178611617;178611616	chr2:179476345;179476344;179476343
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-11
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0923
• Predicted PPI site: N

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
I/V	rs763229497	-1.228	0.333	N	0.165	0.125	0.374076547971	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs763229497	-1.228	0.333	N	0.165	0.125	0.374076547971	gnomAD-4.0.0	1.59285E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43336E-05	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
I/A	0.8763	likely_pathogenic	0.902	pathogenic	-2.834	Highly Destabilizing	0.992	D	0.705	prob.neutral	None	None	None	None	N
I/C	0.9631	likely_pathogenic	0.9703	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
I/D	0.9995	likely_pathogenic	0.9995	pathogenic	-3.735	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
I/E	0.9983	likely_pathogenic	0.9982	pathogenic	-3.434	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
I/F	0.5923	likely_pathogenic	0.649	pathogenic	-1.731	Destabilizing	0.998	D	0.654	neutral	D	0.538603086	None	None	N
I/G	0.9936	likely_pathogenic	0.9951	pathogenic	-3.425	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
I/H	0.9982	likely_pathogenic	0.9981	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
I/K	0.9973	likely_pathogenic	0.9967	pathogenic	-2.427	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
I/L	0.2119	likely_benign	0.2215	benign	-1.067	Destabilizing	0.889	D	0.363	neutral	N	0.412910645	None	None	N
I/M	0.2551	likely_benign	0.2644	benign	-1.114	Destabilizing	0.998	D	0.643	neutral	N	0.475792113	None	None	N
I/N	0.9948	likely_pathogenic	0.9945	pathogenic	-3.078	Highly Destabilizing	0.999	D	0.909	deleterious	D	0.647305898	None	None	N
I/P	0.9968	likely_pathogenic	0.9968	pathogenic	-1.646	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
I/Q	0.997	likely_pathogenic	0.9968	pathogenic	-2.789	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
I/R	0.9949	likely_pathogenic	0.9946	pathogenic	-2.291	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
I/S	0.9817	likely_pathogenic	0.9832	pathogenic	-3.636	Highly Destabilizing	0.998	D	0.845	deleterious	D	0.608639731	None	None	N
I/T	0.9245	likely_pathogenic	0.9323	pathogenic	-3.182	Highly Destabilizing	0.989	D	0.734	prob.delet.	D	0.608639731	None	None	N
I/V	0.1027	likely_benign	0.1192	benign	-1.646	Destabilizing	0.333	N	0.165	neutral	N	0.453669184	None	None	N
I/W	0.9954	likely_pathogenic	0.9959	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/Y	0.9829	likely_pathogenic	0.9844	pathogenic	-1.98	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N

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.