TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8655	26188;26189;26190	chr2:178715223;178715222;178715221	chr2:179579950;179579949;179579948
N2AB	8338	25237;25238;25239	chr2:178715223;178715222;178715221	chr2:179579950;179579949;179579948
N2A	7411	22456;22457;22458	chr2:178715223;178715222;178715221	chr2:179579950;179579949;179579948
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-72
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.8769
• 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
L/P	rs759578526	-0.495	1.0	D	0.723	0.568	0.858636765436	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
L/P	rs759578526	-0.495	1.0	D	0.723	0.568	0.858636765436	gnomAD-4.0.0	1.36866E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79914E-06	0	0
L/R	None	None	1.0	N	0.717	0.43	0.832531937271	gnomAD-4.0.0	6.84328E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99569E-07	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
L/A	0.2075	likely_benign	0.2475	benign	-0.731	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
L/C	0.5131	ambiguous	0.5957	pathogenic	-0.704	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
L/D	0.6663	likely_pathogenic	0.7117	pathogenic	-0.018	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
L/E	0.3207	likely_benign	0.3614	ambiguous	-0.082	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
L/F	0.1459	likely_benign	0.1652	benign	-0.558	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
L/G	0.4245	ambiguous	0.4898	ambiguous	-0.936	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
L/H	0.2611	likely_benign	0.2992	benign	-0.161	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
L/I	0.0932	likely_benign	0.0937	benign	-0.299	Destabilizing	0.994	D	0.611	neutral	None	None	None	None	I
L/K	0.2476	likely_benign	0.2772	benign	-0.416	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
L/M	0.1052	likely_benign	0.1129	benign	-0.396	Destabilizing	0.999	D	0.633	neutral	D	0.527170935	None	None	I
L/N	0.3714	ambiguous	0.3888	ambiguous	-0.248	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
L/P	0.2914	likely_benign	0.3212	benign	-0.409	Destabilizing	1.0	D	0.723	prob.delet.	D	0.533904906	None	None	I
L/Q	0.1278	likely_benign	0.1455	benign	-0.428	Destabilizing	1.0	D	0.709	prob.delet.	N	0.48498154	None	None	I
L/R	0.1808	likely_benign	0.2083	benign	0.105	Stabilizing	1.0	D	0.717	prob.delet.	N	0.511777408	None	None	I
L/S	0.2105	likely_benign	0.2624	benign	-0.78	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
L/T	0.1901	likely_benign	0.2203	benign	-0.728	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
L/V	0.0818	likely_benign	0.0861	benign	-0.409	Destabilizing	0.994	D	0.641	neutral	N	0.466487835	None	None	I
L/W	0.2432	likely_benign	0.2969	benign	-0.577	Destabilizing	0.904	D	0.579	neutral	None	None	None	None	I
L/Y	0.3739	ambiguous	0.4129	ambiguous	-0.335	Destabilizing	0.993	D	0.65	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.