TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6949	21070;21071;21072	chr2:178724530;178724529;178724528	chr2:179589257;179589256;179589255
N2AB	6632	20119;20120;20121	chr2:178724530;178724529;178724528	chr2:179589257;179589256;179589255
N2A	5705	17338;17339;17340	chr2:178724530;178724529;178724528	chr2:179589257;179589256;179589255
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-54
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5127
• 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/L	None	None	0.27	N	0.316	0.08	0.152612264143	gnomAD-4.0.0	6.9812E-07	None	None	None	None	N	None	0	0	None	4.0235E-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
V/A	0.1101	likely_benign	0.1117	benign	-0.683	Destabilizing	0.01	N	0.132	neutral	N	0.456323117	None	None	N
V/C	0.636	likely_pathogenic	0.6304	pathogenic	-0.795	Destabilizing	0.995	D	0.446	neutral	None	None	None	None	N
V/D	0.199	likely_benign	0.2088	benign	-0.066	Destabilizing	0.006	N	0.393	neutral	N	0.479295977	None	None	N
V/E	0.147	likely_benign	0.1541	benign	-0.129	Destabilizing	0.031	N	0.371	neutral	None	None	None	None	N
V/F	0.1183	likely_benign	0.1242	benign	-0.603	Destabilizing	0.927	D	0.476	neutral	N	0.509445526	None	None	N
V/G	0.1548	likely_benign	0.1696	benign	-0.89	Destabilizing	0.27	N	0.414	neutral	N	0.477389036	None	None	N
V/H	0.3545	ambiguous	0.3456	ambiguous	-0.381	Destabilizing	0.981	D	0.47	neutral	None	None	None	None	N
V/I	0.0692	likely_benign	0.0713	benign	-0.269	Destabilizing	0.642	D	0.357	neutral	N	0.471927288	None	None	N
V/K	0.1778	likely_benign	0.1746	benign	-0.548	Destabilizing	0.013	N	0.323	neutral	None	None	None	None	N
V/L	0.1208	likely_benign	0.1239	benign	-0.269	Destabilizing	0.27	N	0.316	neutral	N	0.44402861	None	None	N
V/M	0.0966	likely_benign	0.0988	benign	-0.385	Destabilizing	0.981	D	0.431	neutral	None	None	None	None	N
V/N	0.1441	likely_benign	0.1461	benign	-0.388	Destabilizing	0.704	D	0.495	neutral	None	None	None	None	N
V/P	0.8149	likely_pathogenic	0.833	pathogenic	-0.37	Destabilizing	0.828	D	0.512	neutral	None	None	None	None	N
V/Q	0.1802	likely_benign	0.1756	benign	-0.556	Destabilizing	0.704	D	0.512	neutral	None	None	None	None	N
V/R	0.1491	likely_benign	0.1471	benign	-0.105	Destabilizing	0.543	D	0.497	neutral	None	None	None	None	N
V/S	0.1271	likely_benign	0.1264	benign	-0.878	Destabilizing	0.329	N	0.373	neutral	None	None	None	None	N
V/T	0.1071	likely_benign	0.1057	benign	-0.827	Destabilizing	0.031	N	0.141	neutral	None	None	None	None	N
V/W	0.6778	likely_pathogenic	0.6787	pathogenic	-0.702	Destabilizing	0.995	D	0.5	neutral	None	None	None	None	N
V/Y	0.3773	ambiguous	0.3683	ambiguous	-0.398	Destabilizing	0.981	D	0.472	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.