TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34419	103480;103481;103482	chr2:178533360;178533359;178533358	chr2:179398087;179398086;179398085
N2AB	32778	98557;98558;98559	chr2:178533360;178533359;178533358	chr2:179398087;179398086;179398085
N2A	31851	95776;95777;95778	chr2:178533360;178533359;178533358	chr2:179398087;179398086;179398085
N2B	25354	76285;76286;76287	chr2:178533360;178533359;178533358	chr2:179398087;179398086;179398085
Novex-1	25479	76660;76661;76662	chr2:178533360;178533359;178533358	chr2:179398087;179398086;179398085
Novex-2	25546	76861;76862;76863	chr2:178533360;178533359;178533358	chr2:179398087;179398086;179398085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-162
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.1376
• 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
Y/F	None	None	0.026	N	0.512	0.294	0.412980791724	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
Y/H	None	None	0.059	N	0.516	0.291	0.309530620856	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
Y/A	0.9316	likely_pathogenic	0.8822	pathogenic	-2.971	Highly Destabilizing	0.959	D	0.674	neutral	None	None	None	None	N
Y/C	0.5166	ambiguous	0.3458	ambiguous	-1.682	Destabilizing	0.999	D	0.767	deleterious	N	0.44817422	None	None	N
Y/D	0.9651	likely_pathogenic	0.9262	pathogenic	-3.55	Highly Destabilizing	0.984	D	0.789	deleterious	N	0.503218061	None	None	N
Y/E	0.9862	likely_pathogenic	0.9709	pathogenic	-3.346	Highly Destabilizing	0.976	D	0.709	prob.delet.	None	None	None	None	N
Y/F	0.1769	likely_benign	0.128	benign	-1.016	Destabilizing	0.026	N	0.512	neutral	N	0.502680709	None	None	N
Y/G	0.9531	likely_pathogenic	0.9254	pathogenic	-3.379	Highly Destabilizing	0.988	D	0.745	deleterious	None	None	None	None	N
Y/H	0.6377	likely_pathogenic	0.44	ambiguous	-2.089	Highly Destabilizing	0.059	N	0.516	neutral	N	0.474147313	None	None	N
Y/I	0.8944	likely_pathogenic	0.8312	pathogenic	-1.608	Destabilizing	0.952	D	0.693	prob.neutral	None	None	None	None	N
Y/K	0.973	likely_pathogenic	0.9506	pathogenic	-2.152	Highly Destabilizing	0.988	D	0.751	deleterious	None	None	None	None	N
Y/L	0.8474	likely_pathogenic	0.7881	pathogenic	-1.608	Destabilizing	0.851	D	0.627	neutral	None	None	None	None	N
Y/M	0.9268	likely_pathogenic	0.8848	pathogenic	-1.331	Destabilizing	0.997	D	0.712	prob.delet.	None	None	None	None	N
Y/N	0.8825	likely_pathogenic	0.7691	pathogenic	-2.971	Highly Destabilizing	0.968	D	0.76	deleterious	N	0.513820422	None	None	N
Y/P	0.9973	likely_pathogenic	0.9954	pathogenic	-2.078	Highly Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
Y/Q	0.9569	likely_pathogenic	0.9091	pathogenic	-2.719	Highly Destabilizing	0.988	D	0.705	prob.neutral	None	None	None	None	N
Y/R	0.9248	likely_pathogenic	0.8701	pathogenic	-1.95	Destabilizing	0.976	D	0.755	deleterious	None	None	None	None	N
Y/S	0.8201	likely_pathogenic	0.7022	pathogenic	-3.265	Highly Destabilizing	0.984	D	0.71	prob.delet.	N	0.479051701	None	None	N
Y/T	0.9082	likely_pathogenic	0.842	pathogenic	-2.943	Highly Destabilizing	0.988	D	0.745	deleterious	None	None	None	None	N
Y/V	0.7908	likely_pathogenic	0.7093	pathogenic	-2.078	Highly Destabilizing	0.919	D	0.674	neutral	None	None	None	None	N
Y/W	0.6946	likely_pathogenic	0.5912	pathogenic	-0.393	Destabilizing	0.999	D	0.671	neutral	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.