TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29871	89836;89837;89838	chr2:178553289;178553288;178553287	chr2:179418016;179418015;179418014
N2AB	28230	84913;84914;84915	chr2:178553289;178553288;178553287	chr2:179418016;179418015;179418014
N2A	27303	82132;82133;82134	chr2:178553289;178553288;178553287	chr2:179418016;179418015;179418014
N2B	20806	62641;62642;62643	chr2:178553289;178553288;178553287	chr2:179418016;179418015;179418014
Novex-1	20931	63016;63017;63018	chr2:178553289;178553288;178553287	chr2:179418016;179418015;179418014
Novex-2	20998	63217;63218;63219	chr2:178553289;178553288;178553287	chr2:179418016;179418015;179418014
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-147
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2133
• 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	0.999	D	0.631	0.437	None	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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
V/A	0.3528	ambiguous	0.3286	benign	-1.702	Destabilizing	0.999	D	0.631	neutral	D	0.541350384	None	None	N
V/C	0.8382	likely_pathogenic	0.8532	pathogenic	-1.2	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/D	0.968	likely_pathogenic	0.9641	pathogenic	-1.559	Destabilizing	1.0	D	0.855	deleterious	D	0.63592176	None	None	N
V/E	0.9175	likely_pathogenic	0.9133	pathogenic	-1.481	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/F	0.5974	likely_pathogenic	0.5876	pathogenic	-1.171	Destabilizing	1.0	D	0.799	deleterious	D	0.566222363	None	None	N
V/G	0.6613	likely_pathogenic	0.6304	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.63592176	None	None	N
V/H	0.9609	likely_pathogenic	0.9635	pathogenic	-1.707	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/I	0.0995	likely_benign	0.0996	benign	-0.634	Destabilizing	0.997	D	0.588	neutral	N	0.464263968	None	None	N
V/K	0.8888	likely_pathogenic	0.896	pathogenic	-1.44	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/L	0.5069	ambiguous	0.5117	ambiguous	-0.634	Destabilizing	0.997	D	0.653	neutral	D	0.55668397	None	None	N
V/M	0.3764	ambiguous	0.3659	ambiguous	-0.516	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
V/N	0.8941	likely_pathogenic	0.8934	pathogenic	-1.362	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/P	0.9264	likely_pathogenic	0.9088	pathogenic	-0.956	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Q	0.8763	likely_pathogenic	0.8813	pathogenic	-1.406	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/R	0.8524	likely_pathogenic	0.8588	pathogenic	-1.047	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/S	0.6443	likely_pathogenic	0.6315	pathogenic	-1.968	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/T	0.5251	ambiguous	0.5186	ambiguous	-1.759	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
V/W	0.9839	likely_pathogenic	0.9825	pathogenic	-1.471	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/Y	0.9204	likely_pathogenic	0.9219	pathogenic	-1.138	Destabilizing	1.0	D	0.787	deleterious	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.