TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34226	102901;102902;102903	chr2:178533939;178533938;178533937	chr2:179398666;179398665;179398664
N2AB	32585	97978;97979;97980	chr2:178533939;178533938;178533937	chr2:179398666;179398665;179398664
N2A	31658	95197;95198;95199	chr2:178533939;178533938;178533937	chr2:179398666;179398665;179398664
N2B	25161	75706;75707;75708	chr2:178533939;178533938;178533937	chr2:179398666;179398665;179398664
Novex-1	25286	76081;76082;76083	chr2:178533939;178533938;178533937	chr2:179398666;179398665;179398664
Novex-2	25353	76282;76283;76284	chr2:178533939;178533938;178533937	chr2:179398666;179398665;179398664
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: Ig-160
• Domain position: 90
• Structural Position: 178
• Q(SASA): 0.1135
• 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	0.997	D	0.759	0.761	0.697533386117	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.8329	likely_pathogenic	0.841	pathogenic	-1.851	Destabilizing	0.999	D	0.749	deleterious	D	0.589729918	None	None	N
V/C	0.9536	likely_pathogenic	0.9593	pathogenic	-1.239	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/D	0.986	likely_pathogenic	0.9854	pathogenic	-1.831	Destabilizing	1.0	D	0.862	deleterious	D	0.590335331	None	None	N
V/E	0.9568	likely_pathogenic	0.9571	pathogenic	-1.764	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/F	0.8035	likely_pathogenic	0.7981	pathogenic	-1.234	Destabilizing	1.0	D	0.88	deleterious	D	0.589729918	None	None	N
V/G	0.8876	likely_pathogenic	0.876	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.827	deleterious	D	0.590335331	None	None	N
V/H	0.9862	likely_pathogenic	0.9854	pathogenic	-1.783	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/I	0.1514	likely_benign	0.1494	benign	-0.836	Destabilizing	0.997	D	0.725	prob.delet.	N	0.504598684	None	None	N
V/K	0.9574	likely_pathogenic	0.9563	pathogenic	-1.527	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/L	0.6432	likely_pathogenic	0.6267	pathogenic	-0.836	Destabilizing	0.997	D	0.759	deleterious	D	0.57146035	None	None	N
V/M	0.7272	likely_pathogenic	0.7255	pathogenic	-0.687	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/N	0.9618	likely_pathogenic	0.9624	pathogenic	-1.412	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/P	0.9669	likely_pathogenic	0.9638	pathogenic	-1.143	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Q	0.9438	likely_pathogenic	0.9452	pathogenic	-1.505	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/R	0.9208	likely_pathogenic	0.9172	pathogenic	-1.077	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/S	0.8929	likely_pathogenic	0.8938	pathogenic	-1.999	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/T	0.8084	likely_pathogenic	0.8274	pathogenic	-1.821	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
V/W	0.9941	likely_pathogenic	0.9938	pathogenic	-1.513	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/Y	0.9759	likely_pathogenic	0.9762	pathogenic	-1.225	Destabilizing	1.0	D	0.887	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.