TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30908	92947;92948;92949	chr2:178548904;178548903;178548902	chr2:179413631;179413630;179413629
N2AB	29267	88024;88025;88026	chr2:178548904;178548903;178548902	chr2:179413631;179413630;179413629
N2A	28340	85243;85244;85245	chr2:178548904;178548903;178548902	chr2:179413631;179413630;179413629
N2B	21843	65752;65753;65754	chr2:178548904;178548903;178548902	chr2:179413631;179413630;179413629
Novex-1	21968	66127;66128;66129	chr2:178548904;178548903;178548902	chr2:179413631;179413630;179413629
Novex-2	22035	66328;66329;66330	chr2:178548904;178548903;178548902	chr2:179413631;179413630;179413629
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-113
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.2068
• 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
C/Y	None	None	0.303	N	0.634	0.248	0.437527004654	gnomAD-4.0.0	1.5912E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85789E-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
C/A	0.1533	likely_benign	0.1412	benign	-1.317	Destabilizing	0.007	N	0.331	neutral	None	None	None	None	I
C/D	0.4374	ambiguous	0.4188	ambiguous	-0.306	Destabilizing	0.039	N	0.653	prob.neutral	None	None	None	None	I
C/E	0.5509	ambiguous	0.5499	ambiguous	-0.227	Destabilizing	0.039	N	0.649	prob.neutral	None	None	None	None	I
C/F	0.1463	likely_benign	0.1369	benign	-0.919	Destabilizing	0.303	N	0.639	neutral	N	0.484931084	None	None	I
C/G	0.105	likely_benign	0.095	benign	-1.593	Destabilizing	0.012	N	0.563	neutral	N	0.403776711	None	None	I
C/H	0.2822	likely_benign	0.2774	benign	-1.837	Destabilizing	0.685	D	0.74	deleterious	None	None	None	None	I
C/I	0.2937	likely_benign	0.2751	benign	-0.63	Destabilizing	0.075	N	0.545	neutral	None	None	None	None	I
C/K	0.4587	ambiguous	0.4731	ambiguous	-0.587	Destabilizing	0.039	N	0.653	prob.neutral	None	None	None	None	I
C/L	0.2773	likely_benign	0.258	benign	-0.63	Destabilizing	0.032	N	0.505	neutral	None	None	None	None	I
C/M	0.3842	ambiguous	0.3634	ambiguous	-0.067	Destabilizing	0.637	D	0.545	neutral	None	None	None	None	I
C/N	0.2483	likely_benign	0.2321	benign	-0.516	Destabilizing	0.039	N	0.653	prob.neutral	None	None	None	None	I
C/P	0.8419	likely_pathogenic	0.8224	pathogenic	-0.832	Destabilizing	0.221	N	0.695	prob.delet.	None	None	None	None	I
C/Q	0.3361	likely_benign	0.3277	benign	-0.504	Destabilizing	0.221	N	0.716	prob.delet.	None	None	None	None	I
C/R	0.2015	likely_benign	0.2153	benign	-0.557	Destabilizing	0.177	N	0.689	prob.delet.	N	0.385903027	None	None	I
C/S	0.1023	likely_benign	0.0932	benign	-0.987	Destabilizing	None	N	0.329	neutral	N	0.262098663	None	None	I
C/T	0.1767	likely_benign	0.16	benign	-0.737	Destabilizing	0.016	N	0.469	neutral	None	None	None	None	I
C/V	0.2267	likely_benign	0.2216	benign	-0.832	Destabilizing	0.075	N	0.583	neutral	None	None	None	None	I
C/W	0.3788	ambiguous	0.3656	ambiguous	-0.965	Destabilizing	0.833	D	0.716	prob.delet.	N	0.485451159	None	None	I
C/Y	0.2007	likely_benign	0.1895	benign	-0.85	Destabilizing	0.303	N	0.634	neutral	N	0.466075964	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.