TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25330	76213;76214;76215	chr2:178570144;178570143;178570142	chr2:179434871;179434870;179434869
N2AB	23689	71290;71291;71292	chr2:178570144;178570143;178570142	chr2:179434871;179434870;179434869
N2A	22762	68509;68510;68511	chr2:178570144;178570143;178570142	chr2:179434871;179434870;179434869
N2B	16265	49018;49019;49020	chr2:178570144;178570143;178570142	chr2:179434871;179434870;179434869
Novex-1	16390	49393;49394;49395	chr2:178570144;178570143;178570142	chr2:179434871;179434870;179434869
Novex-2	16457	49594;49595;49596	chr2:178570144;178570143;178570142	chr2:179434871;179434870;179434869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-72
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.3677
• 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
S/A	None	None	0.052	N	0.422	0.101	0.152612264143	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
S/A	0.0797	likely_benign	0.0983	benign	-0.395	Destabilizing	0.052	N	0.422	neutral	N	0.511878116	None	None	I
S/C	0.0966	likely_benign	0.1283	benign	-0.24	Destabilizing	0.915	D	0.387	neutral	N	0.481088794	None	None	I
S/D	0.3237	likely_benign	0.3754	ambiguous	-0.076	Destabilizing	0.081	N	0.369	neutral	None	None	None	None	I
S/E	0.4478	ambiguous	0.5281	ambiguous	-0.178	Destabilizing	0.149	N	0.372	neutral	None	None	None	None	I
S/F	0.1044	likely_benign	0.1928	benign	-1.044	Destabilizing	None	N	0.16	neutral	N	0.50370135	None	None	I
S/G	0.1037	likely_benign	0.1151	benign	-0.49	Destabilizing	0.067	N	0.359	neutral	None	None	None	None	I
S/H	0.2415	likely_benign	0.3382	benign	-1.01	Destabilizing	0.38	N	0.422	neutral	None	None	None	None	I
S/I	0.1801	likely_benign	0.2611	benign	-0.274	Destabilizing	0.081	N	0.541	neutral	None	None	None	None	I
S/K	0.5095	ambiguous	0.6088	pathogenic	-0.491	Destabilizing	0.149	N	0.373	neutral	None	None	None	None	I
S/L	0.1056	likely_benign	0.1251	benign	-0.274	Destabilizing	0.035	N	0.491	neutral	None	None	None	None	I
S/M	0.167	likely_benign	0.2294	benign	0.078	Stabilizing	0.555	D	0.398	neutral	None	None	None	None	I
S/N	0.1127	likely_benign	0.1345	benign	-0.207	Destabilizing	0.001	N	0.075	neutral	None	None	None	None	I
S/P	0.875	likely_pathogenic	0.8759	pathogenic	-0.287	Destabilizing	0.741	D	0.441	neutral	N	0.466009506	None	None	I
S/Q	0.4043	ambiguous	0.5131	ambiguous	-0.505	Destabilizing	0.555	D	0.387	neutral	None	None	None	None	I
S/R	0.4611	ambiguous	0.5346	ambiguous	-0.234	Destabilizing	0.555	D	0.451	neutral	None	None	None	None	I
S/T	0.0831	likely_benign	0.0908	benign	-0.309	Destabilizing	0.052	N	0.379	neutral	N	0.484768873	None	None	I
S/V	0.1515	likely_benign	0.2193	benign	-0.287	Destabilizing	0.081	N	0.521	neutral	None	None	None	None	I
S/W	0.3012	likely_benign	0.4092	ambiguous	-1.046	Destabilizing	0.824	D	0.504	neutral	None	None	None	None	I
S/Y	0.1401	likely_benign	0.2079	benign	-0.767	Destabilizing	None	N	0.303	neutral	N	0.489251973	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.