TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25308	76147;76148;76149	chr2:178570210;178570209;178570208	chr2:179434937;179434936;179434935
N2AB	23667	71224;71225;71226	chr2:178570210;178570209;178570208	chr2:179434937;179434936;179434935
N2A	22740	68443;68444;68445	chr2:178570210;178570209;178570208	chr2:179434937;179434936;179434935
N2B	16243	48952;48953;48954	chr2:178570210;178570209;178570208	chr2:179434937;179434936;179434935
Novex-1	16368	49327;49328;49329	chr2:178570210;178570209;178570208	chr2:179434937;179434936;179434935
Novex-2	16435	49528;49529;49530	chr2:178570210;178570209;178570208	chr2:179434937;179434936;179434935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-72
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1016
• 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
P/L	rs776006935	-0.847	1.0	D	0.91	0.708	0.802005686957	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
P/L	rs776006935	-0.847	1.0	D	0.91	0.708	0.802005686957	gnomAD-4.0.0	6.36791E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14372E-05	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
P/A	0.7325	likely_pathogenic	0.7055	pathogenic	-1.967	Destabilizing	1.0	D	0.812	deleterious	D	0.546942352	None	None	N
P/C	0.8969	likely_pathogenic	0.9164	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/D	0.9989	likely_pathogenic	0.9985	pathogenic	-3.484	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/E	0.9965	likely_pathogenic	0.9959	pathogenic	-3.349	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/F	0.9968	likely_pathogenic	0.9971	pathogenic	-1.183	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/G	0.9812	likely_pathogenic	0.9757	pathogenic	-2.381	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/H	0.9949	likely_pathogenic	0.994	pathogenic	-1.899	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/I	0.9276	likely_pathogenic	0.9521	pathogenic	-0.838	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
P/K	0.9975	likely_pathogenic	0.9972	pathogenic	-1.794	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/L	0.8198	likely_pathogenic	0.8373	pathogenic	-0.838	Destabilizing	1.0	D	0.91	deleterious	D	0.569059078	None	None	N
P/M	0.9533	likely_pathogenic	0.9664	pathogenic	-1.191	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/N	0.9975	likely_pathogenic	0.9969	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/Q	0.9884	likely_pathogenic	0.9867	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.58218981	None	None	N
P/R	0.992	likely_pathogenic	0.9906	pathogenic	-1.439	Destabilizing	1.0	D	0.927	deleterious	D	0.581682831	None	None	N
P/S	0.9583	likely_pathogenic	0.9412	pathogenic	-2.608	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.570580015	None	None	N
P/T	0.9216	likely_pathogenic	0.9134	pathogenic	-2.356	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.569819547	None	None	N
P/V	0.7923	likely_pathogenic	0.8504	pathogenic	-1.189	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/W	0.9993	likely_pathogenic	0.9992	pathogenic	-1.619	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/Y	0.9987	likely_pathogenic	0.9988	pathogenic	-1.319	Destabilizing	1.0	D	0.925	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.