TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6466	19621;19622;19623	chr2:178728530;178728529;178728528	chr2:179593257;179593256;179593255
N2AB	6149	18670;18671;18672	chr2:178728530;178728529;178728528	chr2:179593257;179593256;179593255
N2A	5222	15889;15890;15891	chr2:178728530;178728529;178728528	chr2:179593257;179593256;179593255
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-48
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1793
• 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
S/G	None	None	0.959	N	0.477	0.37	0.254244900254	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.0886	likely_benign	0.0926	benign	-0.675	Destabilizing	0.733	D	0.395	neutral	None	None	None	None	N
S/C	0.1399	likely_benign	0.1518	benign	-0.528	Destabilizing	0.035	N	0.293	neutral	D	0.536118492	None	None	N
S/D	0.3304	likely_benign	0.3462	ambiguous	-0.026	Destabilizing	0.969	D	0.553	neutral	None	None	None	None	N
S/E	0.6305	likely_pathogenic	0.6201	pathogenic	-0.049	Destabilizing	0.969	D	0.553	neutral	None	None	None	None	N
S/F	0.3279	likely_benign	0.3256	benign	-0.952	Destabilizing	0.997	D	0.633	neutral	None	None	None	None	N
S/G	0.1528	likely_benign	0.145	benign	-0.896	Destabilizing	0.959	D	0.477	neutral	N	0.496519337	None	None	N
S/H	0.4685	ambiguous	0.4789	ambiguous	-1.372	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
S/I	0.2783	likely_benign	0.2607	benign	-0.203	Destabilizing	0.976	D	0.621	neutral	N	0.507489096	None	None	N
S/K	0.816	likely_pathogenic	0.8101	pathogenic	-0.649	Destabilizing	0.969	D	0.552	neutral	None	None	None	None	N
S/L	0.176	likely_benign	0.1715	benign	-0.203	Destabilizing	0.939	D	0.573	neutral	None	None	None	None	N
S/M	0.3506	ambiguous	0.357	ambiguous	0.015	Stabilizing	0.997	D	0.555	neutral	None	None	None	None	N
S/N	0.2023	likely_benign	0.1882	benign	-0.564	Destabilizing	0.959	D	0.562	neutral	N	0.495505379	None	None	N
S/P	0.9627	likely_pathogenic	0.9599	pathogenic	-0.327	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	N
S/Q	0.6402	likely_pathogenic	0.6262	pathogenic	-0.73	Destabilizing	0.997	D	0.566	neutral	None	None	None	None	N
S/R	0.7331	likely_pathogenic	0.7122	pathogenic	-0.529	Destabilizing	0.988	D	0.588	neutral	N	0.487845604	None	None	N
S/T	0.1183	likely_benign	0.1206	benign	-0.618	Destabilizing	0.134	N	0.186	neutral	N	0.51181748	None	None	N
S/V	0.2439	likely_benign	0.245	benign	-0.327	Destabilizing	0.939	D	0.605	neutral	None	None	None	None	N
S/W	0.6353	likely_pathogenic	0.61	pathogenic	-0.91	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
S/Y	0.3068	likely_benign	0.2926	benign	-0.645	Destabilizing	0.997	D	0.623	neutral	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.