TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5696	17311;17312;17313	chr2:178731789;178731788;178731787	chr2:179596516;179596515;179596514
N2AB	5379	16360;16361;16362	chr2:178731789;178731788;178731787	chr2:179596516;179596515;179596514
N2A	4452	13579;13580;13581	chr2:178731789;178731788;178731787	chr2:179596516;179596515;179596514
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-40
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0641
• 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
I/F	None	None	0.497	D	0.689	0.526	0.433047596574	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.8066	likely_pathogenic	0.8724	pathogenic	-2.961	Highly Destabilizing	0.157	N	0.687	prob.neutral	None	None	None	None	N
I/C	0.8523	likely_pathogenic	0.8817	pathogenic	-1.93	Destabilizing	0.909	D	0.759	deleterious	None	None	None	None	N
I/D	0.9818	likely_pathogenic	0.9905	pathogenic	-3.387	Highly Destabilizing	0.726	D	0.863	deleterious	None	None	None	None	N
I/E	0.9707	likely_pathogenic	0.9832	pathogenic	-3.071	Highly Destabilizing	0.726	D	0.856	deleterious	None	None	None	None	N
I/F	0.3326	likely_benign	0.3763	ambiguous	-1.643	Destabilizing	0.497	N	0.689	prob.neutral	D	0.559023464	None	None	N
I/G	0.9309	likely_pathogenic	0.9644	pathogenic	-3.529	Highly Destabilizing	0.726	D	0.847	deleterious	None	None	None	None	N
I/H	0.9353	likely_pathogenic	0.9553	pathogenic	-3.115	Highly Destabilizing	0.968	D	0.855	deleterious	None	None	None	None	N
I/K	0.9525	likely_pathogenic	0.9689	pathogenic	-2.113	Highly Destabilizing	0.726	D	0.857	deleterious	None	None	None	None	N
I/L	0.1902	likely_benign	0.2128	benign	-1.22	Destabilizing	0.025	N	0.399	neutral	D	0.534869416	None	None	N
I/M	0.2129	likely_benign	0.2222	benign	-1.493	Destabilizing	0.497	N	0.665	neutral	D	0.605981444	None	None	N
I/N	0.8271	likely_pathogenic	0.8692	pathogenic	-2.834	Highly Destabilizing	0.859	D	0.868	deleterious	D	0.61668066	None	None	N
I/P	0.973	likely_pathogenic	0.9866	pathogenic	-1.797	Destabilizing	0.89	D	0.863	deleterious	None	None	None	None	N
I/Q	0.9428	likely_pathogenic	0.9627	pathogenic	-2.457	Highly Destabilizing	0.89	D	0.878	deleterious	None	None	None	None	N
I/R	0.9346	likely_pathogenic	0.9593	pathogenic	-2.227	Highly Destabilizing	0.726	D	0.867	deleterious	None	None	None	None	N
I/S	0.8421	likely_pathogenic	0.8889	pathogenic	-3.293	Highly Destabilizing	0.497	N	0.805	deleterious	D	0.61668066	None	None	N
I/T	0.8575	likely_pathogenic	0.9037	pathogenic	-2.825	Highly Destabilizing	0.124	N	0.743	deleterious	D	0.606990465	None	None	N
I/V	0.0809	likely_benign	0.1051	benign	-1.797	Destabilizing	None	N	0.275	neutral	D	0.535737354	None	None	N
I/W	0.9581	likely_pathogenic	0.972	pathogenic	-1.901	Destabilizing	0.968	D	0.854	deleterious	None	None	None	None	N
I/Y	0.8023	likely_pathogenic	0.8256	pathogenic	-1.869	Destabilizing	0.726	D	0.758	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.