TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	985	3178;3179;3180	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678
N2AB	985	3178;3179;3180	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678
N2A	985	3178;3179;3180	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678
N2B	939	3040;3041;3042	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678
Novex-1	939	3040;3041;3042	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678
Novex-2	939	3040;3041;3042	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678
Novex-3	985	3178;3179;3180	chr2:178782953;178782952;178782951	chr2:179647680;179647679;179647678

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-3
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.605
• 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/R	None	None	0.009	N	0.231	0.333	0.271763555656	gnomAD-4.0.0	1.59053E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85657E-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	0.1957	likely_benign	0.218	benign	-0.24	Destabilizing	0.25	N	0.374	neutral	None	None	None	None	I
S/C	0.5429	ambiguous	0.5837	pathogenic	-0.299	Destabilizing	0.009	N	0.324	neutral	D	0.551943307	None	None	I
S/D	0.5169	ambiguous	0.5482	ambiguous	0.345	Stabilizing	0.447	N	0.277	neutral	None	None	None	None	I
S/E	0.7032	likely_pathogenic	0.7546	pathogenic	0.253	Stabilizing	0.617	D	0.269	neutral	None	None	None	None	I
S/F	0.8315	likely_pathogenic	0.8683	pathogenic	-0.889	Destabilizing	0.92	D	0.423	neutral	None	None	None	None	I
S/G	0.1679	likely_benign	0.1849	benign	-0.334	Destabilizing	0.201	N	0.274	neutral	N	0.514003389	None	None	I
S/H	0.633	likely_pathogenic	0.6792	pathogenic	-0.79	Destabilizing	0.92	D	0.367	neutral	None	None	None	None	I
S/I	0.7168	likely_pathogenic	0.7813	pathogenic	-0.125	Destabilizing	0.81	D	0.42	neutral	N	0.516425979	None	None	I
S/K	0.8465	likely_pathogenic	0.8859	pathogenic	-0.338	Destabilizing	0.447	N	0.282	neutral	None	None	None	None	I
S/L	0.4577	ambiguous	0.5056	ambiguous	-0.125	Destabilizing	0.447	N	0.397	neutral	None	None	None	None	I
S/M	0.5769	likely_pathogenic	0.6379	pathogenic	-0.052	Destabilizing	0.992	D	0.369	neutral	None	None	None	None	I
S/N	0.1549	likely_benign	0.1669	benign	-0.111	Destabilizing	0.004	N	0.217	neutral	N	0.497580667	None	None	I
S/P	0.4118	ambiguous	0.3971	ambiguous	-0.135	Destabilizing	0.972	D	0.357	neutral	None	None	None	None	I
S/Q	0.7106	likely_pathogenic	0.7619	pathogenic	-0.307	Destabilizing	0.85	D	0.325	neutral	None	None	None	None	I
S/R	0.824	likely_pathogenic	0.8684	pathogenic	-0.179	Destabilizing	0.009	N	0.231	neutral	N	0.516140575	None	None	I
S/T	0.1882	likely_benign	0.2132	benign	-0.211	Destabilizing	0.549	D	0.324	neutral	N	0.494409306	None	None	I
S/V	0.6899	likely_pathogenic	0.7521	pathogenic	-0.135	Destabilizing	0.739	D	0.393	neutral	None	None	None	None	I
S/W	0.854	likely_pathogenic	0.8838	pathogenic	-0.939	Destabilizing	0.992	D	0.547	neutral	None	None	None	None	I
S/Y	0.6277	likely_pathogenic	0.6759	pathogenic	-0.625	Destabilizing	0.972	D	0.423	neutral	None	None	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.