TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21944	66055;66056;66057	chr2:178582973;178582972;178582971	chr2:179447700;179447699;179447698
N2AB	20303	61132;61133;61134	chr2:178582973;178582972;178582971	chr2:179447700;179447699;179447698
N2A	19376	58351;58352;58353	chr2:178582973;178582972;178582971	chr2:179447700;179447699;179447698
N2B	12879	38860;38861;38862	chr2:178582973;178582972;178582971	chr2:179447700;179447699;179447698
Novex-1	13004	39235;39236;39237	chr2:178582973;178582972;178582971	chr2:179447700;179447699;179447698
Novex-2	13071	39436;39437;39438	chr2:178582973;178582972;178582971	chr2:179447700;179447699;179447698
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: Ig-125
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.4934
• 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
S/C	None	None	0.997	D	0.625	0.423	0.495573750707	gnomAD-4.0.0	1.76804E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.16274E-06	0	0
S/Y	None	None	0.99	D	0.713	0.435	0.622510390952	gnomAD-4.0.0	1.76804E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.75371E-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
S/A	0.0962	likely_benign	0.1043	benign	-0.305	Destabilizing	0.656	D	0.459	neutral	N	0.49734946	None	None	N
S/C	0.0917	likely_benign	0.0874	benign	-0.224	Destabilizing	0.997	D	0.625	neutral	D	0.527731082	None	None	N
S/D	0.5063	ambiguous	0.5135	ambiguous	-0.111	Destabilizing	0.926	D	0.47	neutral	None	None	None	None	N
S/E	0.4412	ambiguous	0.4307	ambiguous	-0.226	Destabilizing	0.86	D	0.487	neutral	None	None	None	None	N
S/F	0.1786	likely_benign	0.1889	benign	-1.016	Destabilizing	0.97	D	0.709	prob.delet.	D	0.525037494	None	None	N
S/G	0.1315	likely_benign	0.143	benign	-0.367	Destabilizing	0.86	D	0.458	neutral	None	None	None	None	N
S/H	0.2876	likely_benign	0.2522	benign	-0.89	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
S/I	0.1326	likely_benign	0.1504	benign	-0.271	Destabilizing	0.754	D	0.621	neutral	None	None	None	None	N
S/K	0.4518	ambiguous	0.4088	ambiguous	-0.436	Destabilizing	0.86	D	0.479	neutral	None	None	None	None	N
S/L	0.1057	likely_benign	0.1149	benign	-0.271	Destabilizing	0.754	D	0.629	neutral	None	None	None	None	N
S/M	0.1574	likely_benign	0.1675	benign	0.038	Stabilizing	0.994	D	0.603	neutral	None	None	None	None	N
S/N	0.1362	likely_benign	0.1433	benign	-0.135	Destabilizing	0.978	D	0.499	neutral	None	None	None	None	N
S/P	0.8264	likely_pathogenic	0.84	pathogenic	-0.257	Destabilizing	0.014	N	0.363	neutral	N	0.487013137	None	None	N
S/Q	0.3484	ambiguous	0.3152	benign	-0.441	Destabilizing	0.978	D	0.493	neutral	None	None	None	None	N
S/R	0.4029	ambiguous	0.3661	ambiguous	-0.189	Destabilizing	0.978	D	0.587	neutral	None	None	None	None	N
S/T	0.0662	likely_benign	0.0763	benign	-0.237	Destabilizing	0.822	D	0.459	neutral	N	0.45954322	None	None	N
S/V	0.1464	likely_benign	0.1615	benign	-0.257	Destabilizing	0.076	N	0.477	neutral	None	None	None	None	N
S/W	0.353	ambiguous	0.3262	benign	-1.044	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
S/Y	0.1994	likely_benign	0.1947	benign	-0.756	Destabilizing	0.99	D	0.713	prob.delet.	D	0.536985284	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.