TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6558	19897;19898;19899	chr2:178728152;178728151;178728150	chr2:179592879;179592878;179592877
N2AB	6241	18946;18947;18948	chr2:178728152;178728151;178728150	chr2:179592879;179592878;179592877
N2A	5314	16165;16166;16167	chr2:178728152;178728151;178728150	chr2:179592879;179592878;179592877
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-49
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.8203
• Predicted PPI site: I

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/I	rs879223660	-0.105	0.001	N	0.247	0.121	None	gnomAD-2.1.1	4.11E-06	None	None	None	None	I	None	6.54E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs879223660	-0.105	0.001	N	0.247	0.121	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	1.20691E-04	0	0	0	0	None	0	0	0	0	0
V/I	rs879223660	-0.105	0.001	N	0.247	0.121	None	gnomAD-4.0.0	3.73447E-06	None	None	None	None	I	None	8.02826E-05	0	None	0	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	0.0984	likely_benign	0.1021	benign	-0.379	Destabilizing	0.003	N	0.107	neutral	N	0.455500051	None	None	I
V/C	0.699	likely_pathogenic	0.725	pathogenic	-0.869	Destabilizing	0.981	D	0.334	neutral	None	None	None	None	I
V/D	0.1432	likely_benign	0.1504	benign	-0.344	Destabilizing	0.002	N	0.317	neutral	None	None	None	None	I
V/E	0.1589	likely_benign	0.1638	benign	-0.461	Destabilizing	0.193	N	0.375	neutral	N	0.484934736	None	None	I
V/F	0.1252	likely_benign	0.1298	benign	-0.77	Destabilizing	0.69	D	0.333	neutral	None	None	None	None	I
V/G	0.1424	likely_benign	0.1531	benign	-0.422	Destabilizing	0.324	N	0.384	neutral	N	0.497674747	None	None	I
V/H	0.3739	ambiguous	0.4083	ambiguous	-0.051	Destabilizing	0.981	D	0.334	neutral	None	None	None	None	I
V/I	0.0753	likely_benign	0.0748	benign	-0.404	Destabilizing	0.001	N	0.247	neutral	N	0.50331264	None	None	I
V/K	0.2035	likely_benign	0.2195	benign	-0.399	Destabilizing	0.008	N	0.299	neutral	None	None	None	None	I
V/L	0.1544	likely_benign	0.1623	benign	-0.404	Destabilizing	0.033	N	0.339	neutral	N	0.517241943	None	None	I
V/M	0.1155	likely_benign	0.1221	benign	-0.598	Destabilizing	0.69	D	0.301	neutral	None	None	None	None	I
V/N	0.1586	likely_benign	0.1725	benign	-0.23	Destabilizing	0.69	D	0.365	neutral	None	None	None	None	I
V/P	0.2931	likely_benign	0.329	benign	-0.369	Destabilizing	0.818	D	0.378	neutral	None	None	None	None	I
V/Q	0.2216	likely_benign	0.2365	benign	-0.435	Destabilizing	0.69	D	0.381	neutral	None	None	None	None	I
V/R	0.1858	likely_benign	0.1956	benign	0.033	Stabilizing	0.527	D	0.365	neutral	None	None	None	None	I
V/S	0.1291	likely_benign	0.1373	benign	-0.542	Destabilizing	0.241	N	0.376	neutral	None	None	None	None	I
V/T	0.1274	likely_benign	0.1268	benign	-0.57	Destabilizing	0.388	N	0.296	neutral	None	None	None	None	I
V/W	0.6472	likely_pathogenic	0.6638	pathogenic	-0.812	Destabilizing	0.981	D	0.461	neutral	None	None	None	None	I
V/Y	0.3972	ambiguous	0.4169	ambiguous	-0.552	Destabilizing	0.818	D	0.331	neutral	None	None	None	None	I

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.