TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1751	5476;5477;5478	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338
N2AB	1751	5476;5477;5478	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338
N2A	1751	5476;5477;5478	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338
N2B	1705	5338;5339;5340	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338
Novex-1	1705	5338;5339;5340	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338
Novex-2	1705	5338;5339;5340	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338
Novex-3	1751	5476;5477;5478	chr2:178776613;178776612;178776611	chr2:179641340;179641339;179641338

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-8
• Domain position: 49
• Structural Position: 121
• Q(SASA): 0.1597
• 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	rs1234295408	None	0.64	N	0.357	0.263	0.462374447365	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs1234295408	None	0.64	N	0.357	0.263	0.462374447365	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	None	0	0	0	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
L/A	0.943	likely_pathogenic	0.9446	pathogenic	-2.175	Highly Destabilizing	0.998	D	0.591	neutral	None	None	None	None	N
L/C	0.9634	likely_pathogenic	0.9624	pathogenic	-1.35	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9982	likely_pathogenic	0.9988	pathogenic	-1.631	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/E	0.9818	likely_pathogenic	0.9879	pathogenic	-1.503	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/F	0.7546	likely_pathogenic	0.7353	pathogenic	-1.335	Destabilizing	0.64	D	0.357	neutral	N	0.422508321	None	None	N
L/G	0.988	likely_pathogenic	0.9897	pathogenic	-2.641	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/H	0.9629	likely_pathogenic	0.9686	pathogenic	-1.891	Destabilizing	1.0	D	0.855	deleterious	N	0.497121485	None	None	N
L/I	0.2996	likely_benign	0.2783	benign	-0.889	Destabilizing	0.996	D	0.49	neutral	N	0.407205951	None	None	N
L/K	0.9584	likely_pathogenic	0.9742	pathogenic	-1.507	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/M	0.418	ambiguous	0.4066	ambiguous	-0.72	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/N	0.9837	likely_pathogenic	0.9867	pathogenic	-1.513	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/P	0.9935	likely_pathogenic	0.9954	pathogenic	-1.292	Destabilizing	1.0	D	0.871	deleterious	N	0.515795597	None	None	N
L/Q	0.9175	likely_pathogenic	0.9401	pathogenic	-1.513	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/R	0.9434	likely_pathogenic	0.9611	pathogenic	-1.098	Destabilizing	1.0	D	0.853	deleterious	N	0.513196832	None	None	N
L/S	0.9829	likely_pathogenic	0.9848	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/T	0.9346	likely_pathogenic	0.9402	pathogenic	-1.999	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/V	0.3841	ambiguous	0.3569	ambiguous	-1.292	Destabilizing	0.996	D	0.473	neutral	N	0.443085517	None	None	N
L/W	0.9413	likely_pathogenic	0.9443	pathogenic	-1.539	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/Y	0.9473	likely_pathogenic	0.9459	pathogenic	-1.282	Destabilizing	0.998	D	0.782	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.