TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17606	53041;53042;53043	chr2:178607971;178607970;178607969	chr2:179472698;179472697;179472696
N2AB	15965	48118;48119;48120	chr2:178607971;178607970;178607969	chr2:179472698;179472697;179472696
N2A	15038	45337;45338;45339	chr2:178607971;178607970;178607969	chr2:179472698;179472697;179472696
N2B	8541	25846;25847;25848	chr2:178607971;178607970;178607969	chr2:179472698;179472697;179472696
Novex-1	8666	26221;26222;26223	chr2:178607971;178607970;178607969	chr2:179472698;179472697;179472696
Novex-2	8733	26422;26423;26424	chr2:178607971;178607970;178607969	chr2:179472698;179472697;179472696
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: Fn3-16
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.099
• 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	rs2055325123	None	0.117	N	0.337	0.141	0.403328974453	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02773E-05

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	0.8146	likely_pathogenic	0.8049	pathogenic	-2.227	Highly Destabilizing	0.977	D	0.641	neutral	D	0.526829272	None	None	N
V/C	0.9674	likely_pathogenic	0.9714	pathogenic	-1.836	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9985	pathogenic	-3.266	Highly Destabilizing	0.999	D	0.889	deleterious	D	0.538946046	None	None	N
V/E	0.993	likely_pathogenic	0.9943	pathogenic	-2.954	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/F	0.901	likely_pathogenic	0.8875	pathogenic	-1.305	Destabilizing	0.993	D	0.845	deleterious	D	0.538692556	None	None	N
V/G	0.9547	likely_pathogenic	0.9579	pathogenic	-2.843	Highly Destabilizing	0.999	D	0.891	deleterious	D	0.538946046	None	None	N
V/H	0.9979	likely_pathogenic	0.998	pathogenic	-2.841	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/I	0.0954	likely_benign	0.0946	benign	-0.447	Destabilizing	0.117	N	0.337	neutral	N	0.471770651	None	None	N
V/K	0.9938	likely_pathogenic	0.9945	pathogenic	-1.854	Destabilizing	0.998	D	0.886	deleterious	None	None	None	None	N
V/L	0.5274	ambiguous	0.5316	ambiguous	-0.447	Destabilizing	0.898	D	0.597	neutral	N	0.475661892	None	None	N
V/M	0.7636	likely_pathogenic	0.725	pathogenic	-0.719	Destabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
V/N	0.995	likely_pathogenic	0.9959	pathogenic	-2.5	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
V/P	0.9872	likely_pathogenic	0.9898	pathogenic	-1.02	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
V/Q	0.9906	likely_pathogenic	0.9913	pathogenic	-2.158	Highly Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
V/R	0.9846	likely_pathogenic	0.9867	pathogenic	-1.951	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
V/S	0.9704	likely_pathogenic	0.973	pathogenic	-3.038	Highly Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
V/T	0.8667	likely_pathogenic	0.8622	pathogenic	-2.562	Highly Destabilizing	0.983	D	0.697	prob.neutral	None	None	None	None	N
V/W	0.998	likely_pathogenic	0.9979	pathogenic	-1.94	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Y	0.994	likely_pathogenic	0.9938	pathogenic	-1.56	Destabilizing	0.999	D	0.844	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.