TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22444	67555;67556;67557	chr2:178579957;178579956;178579955	chr2:179444684;179444683;179444682
N2AB	20803	62632;62633;62634	chr2:178579957;178579956;178579955	chr2:179444684;179444683;179444682
N2A	19876	59851;59852;59853	chr2:178579957;178579956;178579955	chr2:179444684;179444683;179444682
N2B	13379	40360;40361;40362	chr2:178579957;178579956;178579955	chr2:179444684;179444683;179444682
Novex-1	13504	40735;40736;40737	chr2:178579957;178579956;178579955	chr2:179444684;179444683;179444682
Novex-2	13571	40936;40937;40938	chr2:178579957;178579956;178579955	chr2:179444684;179444683;179444682
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-50
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.787
• 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
D/E	None	None	0.919	N	0.441	0.17	0.297031009988	gnomAD-4.0.0	6.84463E-07	None	None	None	None	N	None	0	0	None	3.83024E-05	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
D/A	0.204	likely_benign	0.1635	benign	-0.115	Destabilizing	0.851	D	0.549	neutral	N	0.51759058	None	None	N
D/C	0.6423	likely_pathogenic	0.5444	ambiguous	-0.258	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
D/E	0.1376	likely_benign	0.1126	benign	-0.242	Destabilizing	0.919	D	0.441	neutral	N	0.38902905	None	None	N
D/F	0.5909	likely_pathogenic	0.5064	ambiguous	-0.042	Destabilizing	0.997	D	0.765	deleterious	None	None	None	None	N
D/G	0.1949	likely_benign	0.1686	benign	-0.262	Destabilizing	0.015	N	0.316	neutral	N	0.493676358	None	None	N
D/H	0.3494	ambiguous	0.2785	benign	0.534	Stabilizing	0.988	D	0.538	neutral	N	0.488353268	None	None	N
D/I	0.3619	ambiguous	0.2891	benign	0.217	Stabilizing	0.997	D	0.765	deleterious	None	None	None	None	N
D/K	0.4478	ambiguous	0.3726	ambiguous	0.312	Stabilizing	0.938	D	0.56	neutral	None	None	None	None	N
D/L	0.3726	ambiguous	0.3121	benign	0.217	Stabilizing	0.991	D	0.745	deleterious	None	None	None	None	N
D/M	0.6141	likely_pathogenic	0.5112	ambiguous	0.013	Stabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
D/N	0.1431	likely_benign	0.1174	benign	-0.023	Destabilizing	0.034	N	0.227	neutral	N	0.503853279	None	None	N
D/P	0.804	likely_pathogenic	0.768	pathogenic	0.127	Stabilizing	0.997	D	0.57	neutral	None	None	None	None	N
D/Q	0.3775	ambiguous	0.3043	benign	0.013	Stabilizing	0.991	D	0.487	neutral	None	None	None	None	N
D/R	0.5101	ambiguous	0.4406	ambiguous	0.619	Stabilizing	0.981	D	0.743	deleterious	None	None	None	None	N
D/S	0.1882	likely_benign	0.1518	benign	-0.121	Destabilizing	0.883	D	0.397	neutral	None	None	None	None	N
D/T	0.2724	likely_benign	0.2098	benign	0.005	Stabilizing	0.938	D	0.581	neutral	None	None	None	None	N
D/V	0.1942	likely_benign	0.1578	benign	0.127	Stabilizing	0.988	D	0.745	deleterious	N	0.474969047	None	None	N
D/W	0.8673	likely_pathogenic	0.8328	pathogenic	0.06	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
D/Y	0.2116	likely_benign	0.1839	benign	0.193	Stabilizing	0.996	D	0.754	deleterious	N	0.498695616	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.