TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28164	84715;84716;84717	chr2:178561642;178561641;178561640	chr2:179426369;179426368;179426367
N2AB	26523	79792;79793;79794	chr2:178561642;178561641;178561640	chr2:179426369;179426368;179426367
N2A	25596	77011;77012;77013	chr2:178561642;178561641;178561640	chr2:179426369;179426368;179426367
N2B	19099	57520;57521;57522	chr2:178561642;178561641;178561640	chr2:179426369;179426368;179426367
Novex-1	19224	57895;57896;57897	chr2:178561642;178561641;178561640	chr2:179426369;179426368;179426367
Novex-2	19291	58096;58097;58098	chr2:178561642;178561641;178561640	chr2:179426369;179426368;179426367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-93
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4467
• 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/G	rs1703698768	None	0.101	N	0.407	0.134	0.589461000006	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	0
V/L	None	None	0.001	N	0.088	0.051	0.251639045875	gnomAD-4.0.0	1.60036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42836E-04	0	0	0
V/M	None	None	0.017	N	0.231	0.058	0.302793454619	gnomAD-4.0.0	1.60036E-06	None	None	None	None	N	None	0	2.3033E-05	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	0.0995	likely_benign	0.0893	benign	-0.706	Destabilizing	0.001	N	0.083	neutral	N	0.454603469	None	None	N
V/C	0.5199	ambiguous	0.4814	ambiguous	-0.604	Destabilizing	0.94	D	0.372	neutral	None	None	None	None	N
V/D	0.2413	likely_benign	0.2024	benign	-0.557	Destabilizing	0.418	N	0.431	neutral	None	None	None	None	N
V/E	0.1859	likely_benign	0.1564	benign	-0.633	Destabilizing	0.351	N	0.384	neutral	N	0.478613692	None	None	N
V/F	0.1249	likely_benign	0.1142	benign	-0.717	Destabilizing	0.716	D	0.453	neutral	None	None	None	None	N
V/G	0.1364	likely_benign	0.1214	benign	-0.898	Destabilizing	0.101	N	0.407	neutral	N	0.511496901	None	None	N
V/H	0.352	ambiguous	0.3061	benign	-0.392	Destabilizing	0.983	D	0.365	neutral	None	None	None	None	N
V/I	0.0685	likely_benign	0.0674	benign	-0.325	Destabilizing	0.129	N	0.333	neutral	None	None	None	None	N
V/K	0.2178	likely_benign	0.1799	benign	-0.676	Destabilizing	0.418	N	0.382	neutral	None	None	None	None	N
V/L	0.1162	likely_benign	0.1024	benign	-0.325	Destabilizing	0.001	N	0.088	neutral	N	0.45685434	None	None	N
V/M	0.099	likely_benign	0.0905	benign	-0.379	Destabilizing	0.017	N	0.231	neutral	N	0.495162012	None	None	N
V/N	0.162	likely_benign	0.1423	benign	-0.418	Destabilizing	0.418	N	0.456	neutral	None	None	None	None	N
V/P	0.6625	likely_pathogenic	0.5648	pathogenic	-0.416	Destabilizing	0.836	D	0.44	neutral	None	None	None	None	N
V/Q	0.1901	likely_benign	0.1621	benign	-0.633	Destabilizing	0.836	D	0.427	neutral	None	None	None	None	N
V/R	0.2071	likely_benign	0.1731	benign	-0.13	Destabilizing	0.716	D	0.446	neutral	None	None	None	None	N
V/S	0.1094	likely_benign	0.1002	benign	-0.797	Destabilizing	0.012	N	0.223	neutral	None	None	None	None	N
V/T	0.0953	likely_benign	0.0868	benign	-0.77	Destabilizing	0.002	N	0.119	neutral	None	None	None	None	N
V/W	0.6305	likely_pathogenic	0.5733	pathogenic	-0.837	Destabilizing	0.983	D	0.398	neutral	None	None	None	None	N
V/Y	0.3395	likely_benign	0.2978	benign	-0.544	Destabilizing	0.836	D	0.396	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.