TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21125	63598;63599;63600	chr2:178588034;178588033;178588032	chr2:179452761;179452760;179452759
N2AB	19484	58675;58676;58677	chr2:178588034;178588033;178588032	chr2:179452761;179452760;179452759
N2A	18557	55894;55895;55896	chr2:178588034;178588033;178588032	chr2:179452761;179452760;179452759
N2B	12060	36403;36404;36405	chr2:178588034;178588033;178588032	chr2:179452761;179452760;179452759
Novex-1	12185	36778;36779;36780	chr2:178588034;178588033;178588032	chr2:179452761;179452760;179452759
Novex-2	12252	36979;36980;36981	chr2:178588034;178588033;178588032	chr2:179452761;179452760;179452759
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-41
• Domain position: 62
• Structural Position: 77
• Q(SASA): 0.1188
• 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
L/F	rs1040226223	-1.78	0.993	N	0.787	0.257	0.40017627803	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66223E-04
L/F	rs1040226223	-1.78	0.993	N	0.787	0.257	0.40017627803	gnomAD-4.0.0	1.59301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.027E-05
L/I	None	None	0.955	N	0.545	0.18	0.31077124679	gnomAD-4.0.0	1.59301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-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
L/A	0.4433	ambiguous	0.4864	ambiguous	-2.072	Highly Destabilizing	0.966	D	0.552	neutral	None	None	None	None	N
L/C	0.6759	likely_pathogenic	0.7201	pathogenic	-1.215	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/D	0.8809	likely_pathogenic	0.8986	pathogenic	-2.049	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
L/E	0.683	likely_pathogenic	0.7028	pathogenic	-1.809	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
L/F	0.3639	ambiguous	0.3956	ambiguous	-1.145	Destabilizing	0.993	D	0.787	deleterious	N	0.452196167	None	None	N
L/G	0.7378	likely_pathogenic	0.774	pathogenic	-2.625	Highly Destabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
L/H	0.5971	likely_pathogenic	0.6465	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.821	deleterious	N	0.463970546	None	None	N
L/I	0.1079	likely_benign	0.1225	benign	-0.484	Destabilizing	0.955	D	0.545	neutral	N	0.442449743	None	None	N
L/K	0.6757	likely_pathogenic	0.6981	pathogenic	-1.362	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
L/M	0.1831	likely_benign	0.1879	benign	-0.453	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
L/N	0.6227	likely_pathogenic	0.6451	pathogenic	-1.708	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
L/P	0.6525	likely_pathogenic	0.6715	pathogenic	-0.993	Destabilizing	0.999	D	0.807	deleterious	N	0.453493456	None	None	N
L/Q	0.4977	ambiguous	0.5206	ambiguous	-1.524	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
L/R	0.5962	likely_pathogenic	0.63	pathogenic	-1.242	Destabilizing	0.997	D	0.785	deleterious	N	0.463210078	None	None	N
L/S	0.6515	likely_pathogenic	0.6886	pathogenic	-2.436	Highly Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
L/T	0.3833	ambiguous	0.4035	ambiguous	-2.042	Highly Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
L/V	0.1022	likely_benign	0.1169	benign	-0.993	Destabilizing	0.117	N	0.434	neutral	N	0.422189114	None	None	N
L/W	0.5593	ambiguous	0.6285	pathogenic	-1.522	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/Y	0.6467	likely_pathogenic	0.6853	pathogenic	-1.164	Destabilizing	0.998	D	0.774	deleterious	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.