TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27027	81304;81305;81306	chr2:178565053;178565052;178565051	chr2:179429780;179429779;179429778
N2AB	25386	76381;76382;76383	chr2:178565053;178565052;178565051	chr2:179429780;179429779;179429778
N2A	24459	73600;73601;73602	chr2:178565053;178565052;178565051	chr2:179429780;179429779;179429778
N2B	17962	54109;54110;54111	chr2:178565053;178565052;178565051	chr2:179429780;179429779;179429778
Novex-1	18087	54484;54485;54486	chr2:178565053;178565052;178565051	chr2:179429780;179429779;179429778
Novex-2	18154	54685;54686;54687	chr2:178565053;178565052;178565051	chr2:179429780;179429779;179429778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-84
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0947
• 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	rs749171660	-1.875	0.489	N	0.534	0.34	0.506311303838	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/A	rs749171660	-1.875	0.489	N	0.534	0.34	0.506311303838	gnomAD-4.0.0	4.10565E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99543E-07	5.79872E-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	0.6465	likely_pathogenic	0.6267	pathogenic	-1.733	Destabilizing	0.489	N	0.534	neutral	N	0.462793502	None	None	N
V/C	0.9531	likely_pathogenic	0.9403	pathogenic	-1.439	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
V/D	0.9935	likely_pathogenic	0.9931	pathogenic	-1.657	Destabilizing	0.942	D	0.735	prob.delet.	N	0.474772145	None	None	N
V/E	0.9737	likely_pathogenic	0.9757	pathogenic	-1.527	Destabilizing	0.956	D	0.697	prob.neutral	None	None	None	None	N
V/F	0.8852	likely_pathogenic	0.8805	pathogenic	-1.122	Destabilizing	0.97	D	0.697	prob.neutral	N	0.47859726	None	None	N
V/G	0.9162	likely_pathogenic	0.9124	pathogenic	-2.189	Highly Destabilizing	0.698	D	0.724	prob.delet.	N	0.474933048	None	None	N
V/H	0.9929	likely_pathogenic	0.9923	pathogenic	-1.805	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
V/I	0.1155	likely_benign	0.0974	benign	-0.522	Destabilizing	0.025	N	0.161	neutral	N	0.481904713	None	None	N
V/K	0.9846	likely_pathogenic	0.9851	pathogenic	-1.358	Destabilizing	0.956	D	0.699	prob.neutral	None	None	None	None	N
V/L	0.7069	likely_pathogenic	0.6228	pathogenic	-0.522	Destabilizing	0.489	N	0.428	neutral	N	0.487329176	None	None	N
V/M	0.5748	likely_pathogenic	0.5187	ambiguous	-0.599	Destabilizing	0.978	D	0.659	neutral	None	None	None	None	N
V/N	0.9563	likely_pathogenic	0.9493	pathogenic	-1.444	Destabilizing	0.956	D	0.761	deleterious	None	None	None	None	N
V/P	0.9894	likely_pathogenic	0.9868	pathogenic	-0.893	Destabilizing	0.978	D	0.722	prob.delet.	None	None	None	None	N
V/Q	0.9637	likely_pathogenic	0.9651	pathogenic	-1.417	Destabilizing	0.956	D	0.713	prob.delet.	None	None	None	None	N
V/R	0.975	likely_pathogenic	0.9772	pathogenic	-1.091	Destabilizing	0.956	D	0.771	deleterious	None	None	None	None	N
V/S	0.8512	likely_pathogenic	0.8356	pathogenic	-2.117	Highly Destabilizing	0.076	N	0.506	neutral	None	None	None	None	N
V/T	0.6422	likely_pathogenic	0.6403	pathogenic	-1.848	Destabilizing	0.754	D	0.605	neutral	None	None	None	None	N
V/W	0.9981	likely_pathogenic	0.9978	pathogenic	-1.459	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/Y	0.9891	likely_pathogenic	0.9874	pathogenic	-1.086	Destabilizing	0.993	D	0.701	prob.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.