TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28688	86287;86288;86289	chr2:178560070;178560069;178560068	chr2:179424797;179424796;179424795
N2AB	27047	81364;81365;81366	chr2:178560070;178560069;178560068	chr2:179424797;179424796;179424795
N2A	26120	78583;78584;78585	chr2:178560070;178560069;178560068	chr2:179424797;179424796;179424795
N2B	19623	59092;59093;59094	chr2:178560070;178560069;178560068	chr2:179424797;179424796;179424795
Novex-1	19748	59467;59468;59469	chr2:178560070;178560069;178560068	chr2:179424797;179424796;179424795
Novex-2	19815	59668;59669;59670	chr2:178560070;178560069;178560068	chr2:179424797;179424796;179424795
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-97
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1073
• 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	N	0.593	0.352	0.571828761226	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.7004	likely_pathogenic	0.6584	pathogenic	-2.124	Highly Destabilizing	0.999	D	0.591	neutral	D	0.552998149	None	None	N
V/C	0.9614	likely_pathogenic	0.9526	pathogenic	-1.57	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/D	0.9981	likely_pathogenic	0.9979	pathogenic	-3.057	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/E	0.9926	likely_pathogenic	0.9919	pathogenic	-2.708	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.553758618	None	None	N
V/F	0.7774	likely_pathogenic	0.7325	pathogenic	-1.16	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/G	0.9395	likely_pathogenic	0.9259	pathogenic	-2.77	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.553758618	None	None	N
V/H	0.9973	likely_pathogenic	0.9965	pathogenic	-2.812	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/I	0.0805	likely_benign	0.0807	benign	-0.233	Destabilizing	0.997	D	0.539	neutral	N	0.494396795	None	None	N
V/K	0.9936	likely_pathogenic	0.9926	pathogenic	-1.605	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/L	0.3511	ambiguous	0.3529	ambiguous	-0.233	Destabilizing	0.997	D	0.593	neutral	N	0.521452897	None	None	N
V/M	0.4391	ambiguous	0.4178	ambiguous	-0.608	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
V/N	0.9929	likely_pathogenic	0.9918	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/P	0.9935	likely_pathogenic	0.9917	pathogenic	-0.846	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/Q	0.9907	likely_pathogenic	0.9891	pathogenic	-1.926	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/R	0.9877	likely_pathogenic	0.9853	pathogenic	-1.939	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/S	0.963	likely_pathogenic	0.9553	pathogenic	-2.868	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/T	0.8207	likely_pathogenic	0.8025	pathogenic	-2.34	Highly Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
V/W	0.9968	likely_pathogenic	0.9952	pathogenic	-1.698	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9855	likely_pathogenic	0.9802	pathogenic	-1.37	Destabilizing	1.0	D	0.799	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.