TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2554	7885;7886;7887	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029
N2AB	2554	7885;7886;7887	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029
N2A	2554	7885;7886;7887	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029
N2B	2508	7747;7748;7749	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029
Novex-1	2508	7747;7748;7749	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029
Novex-2	2508	7747;7748;7749	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029
Novex-3	2554	7885;7886;7887	chr2:178773304;178773303;178773302	chr2:179638031;179638030;179638029

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-15
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0562
• 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/I	None	None	0.997	N	0.547	0.259	0.404315859256	gnomAD-4.0.0	6.84144E-07	None	None	None	None	N	None	0	2.23704E-05	None	0	0	None	0	0	0	0	0
V/L	None	None	0.997	N	0.659	0.259	0.348764635752	gnomAD-4.0.0	6.84144E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99327E-07	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	0.2963	likely_benign	0.3233	benign	-2.387	Highly Destabilizing	0.999	D	0.664	neutral	N	0.497249853	None	None	N
V/C	0.8906	likely_pathogenic	0.8749	pathogenic	-1.694	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/D	0.9862	likely_pathogenic	0.9828	pathogenic	-3.377	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.601570768	None	None	N
V/E	0.974	likely_pathogenic	0.9696	pathogenic	-3.051	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
V/F	0.9203	likely_pathogenic	0.8815	pathogenic	-1.374	Destabilizing	1.0	D	0.856	deleterious	D	0.601418883	None	None	N
V/G	0.6046	likely_pathogenic	0.5967	pathogenic	-2.989	Highly Destabilizing	1.0	D	0.903	deleterious	D	0.538102589	None	None	N
V/H	0.9965	likely_pathogenic	0.9952	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/I	0.2181	likely_benign	0.1946	benign	-0.623	Destabilizing	0.997	D	0.547	neutral	N	0.479981992	None	None	N
V/K	0.99	likely_pathogenic	0.9875	pathogenic	-1.956	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/L	0.8366	likely_pathogenic	0.7978	pathogenic	-0.623	Destabilizing	0.997	D	0.659	neutral	N	0.503247197	None	None	N
V/M	0.7067	likely_pathogenic	0.6421	pathogenic	-0.861	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/N	0.9504	likely_pathogenic	0.9436	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
V/P	0.9946	likely_pathogenic	0.9942	pathogenic	-1.195	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/Q	0.9819	likely_pathogenic	0.9775	pathogenic	-2.309	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
V/R	0.9831	likely_pathogenic	0.9775	pathogenic	-2.068	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
V/S	0.689	likely_pathogenic	0.7092	pathogenic	-3.151	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/T	0.3798	ambiguous	0.4117	ambiguous	-2.668	Highly Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9982	pathogenic	-1.924	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/Y	0.9883	likely_pathogenic	0.9839	pathogenic	-1.619	Destabilizing	1.0	D	0.857	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.