TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2184	6775;6776;6777	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886
N2AB	2184	6775;6776;6777	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886
N2A	2184	6775;6776;6777	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886
N2B	2138	6637;6638;6639	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886
Novex-1	2138	6637;6638;6639	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886
Novex-2	2138	6637;6638;6639	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886
Novex-3	2184	6775;6776;6777	chr2:178775161;178775160;178775159	chr2:179639888;179639887;179639886

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-11
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5244
• 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
V/A	None	None	None	N	0.069	0.136	0.302793454619	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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
V/A	0.1106	likely_benign	0.1066	benign	-0.837	Destabilizing	None	N	0.069	neutral	N	0.498845922	None	None	N
V/C	0.5953	likely_pathogenic	0.592	pathogenic	-0.807	Destabilizing	0.665	D	0.33	neutral	None	None	None	None	N
V/D	0.2363	likely_benign	0.2181	benign	-0.779	Destabilizing	0.174	N	0.335	neutral	N	0.502778739	None	None	N
V/E	0.1527	likely_benign	0.1439	benign	-0.849	Destabilizing	0.103	N	0.285	neutral	None	None	None	None	N
V/F	0.1166	likely_benign	0.113	benign	-0.778	Destabilizing	0.095	N	0.373	neutral	N	0.512934434	None	None	N
V/G	0.2011	likely_benign	0.191	benign	-1.034	Destabilizing	0.042	N	0.267	neutral	N	0.515941783	None	None	N
V/H	0.2903	likely_benign	0.2777	benign	-0.48	Destabilizing	0.495	N	0.346	neutral	None	None	None	None	N
V/I	0.0672	likely_benign	0.0669	benign	-0.439	Destabilizing	0.08	N	0.226	neutral	N	0.498308001	None	None	N
V/K	0.1445	likely_benign	0.1404	benign	-0.919	Destabilizing	0.103	N	0.291	neutral	None	None	None	None	N
V/L	0.1268	likely_benign	0.1212	benign	-0.439	Destabilizing	0.019	N	0.213	neutral	N	0.506729759	None	None	N
V/M	0.0992	likely_benign	0.0958	benign	-0.494	Destabilizing	0.858	D	0.28	neutral	None	None	None	None	N
V/N	0.1437	likely_benign	0.1353	benign	-0.722	Destabilizing	0.218	N	0.397	neutral	None	None	None	None	N
V/P	0.4464	ambiguous	0.4312	ambiguous	-0.536	Destabilizing	None	N	0.174	neutral	None	None	None	None	N
V/Q	0.172	likely_benign	0.165	benign	-0.938	Destabilizing	0.362	N	0.396	neutral	None	None	None	None	N
V/R	0.1471	likely_benign	0.144	benign	-0.323	Destabilizing	0.218	N	0.428	neutral	None	None	None	None	N
V/S	0.1215	likely_benign	0.116	benign	-1.091	Destabilizing	0.005	N	0.16	neutral	None	None	None	None	N
V/T	0.0803	likely_benign	0.0791	benign	-1.063	Destabilizing	0.001	N	0.064	neutral	None	None	None	None	N
V/W	0.6401	likely_pathogenic	0.6202	pathogenic	-0.891	Destabilizing	0.882	D	0.327	neutral	None	None	None	None	N
V/Y	0.3328	likely_benign	0.3205	benign	-0.62	Destabilizing	0.004	N	0.242	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.