TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27811	83656;83657;83658	chr2:178562701;178562700;178562699	chr2:179427428;179427427;179427426
N2AB	26170	78733;78734;78735	chr2:178562701;178562700;178562699	chr2:179427428;179427427;179427426
N2A	25243	75952;75953;75954	chr2:178562701;178562700;178562699	chr2:179427428;179427427;179427426
N2B	18746	56461;56462;56463	chr2:178562701;178562700;178562699	chr2:179427428;179427427;179427426
Novex-1	18871	56836;56837;56838	chr2:178562701;178562700;178562699	chr2:179427428;179427427;179427426
Novex-2	18938	57037;57038;57039	chr2:178562701;178562700;178562699	chr2:179427428;179427427;179427426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-90
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0105
• 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
K/N	None	None	0.998	N	0.421	0.255	0.270001397563	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.922	likely_pathogenic	0.9386	pathogenic	-0.084	Destabilizing	0.94	D	0.42	neutral	None	None	None	None	N
K/C	0.9711	likely_pathogenic	0.9744	pathogenic	-0.61	Destabilizing	1.0	D	0.441	neutral	None	None	None	None	N
K/D	0.982	likely_pathogenic	0.988	pathogenic	-0.442	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	N
K/E	0.9044	likely_pathogenic	0.9358	pathogenic	-0.466	Destabilizing	0.981	D	0.413	neutral	N	0.504874786	None	None	N
K/F	0.9832	likely_pathogenic	0.9865	pathogenic	-0.469	Destabilizing	0.981	D	0.451	neutral	None	None	None	None	N
K/G	0.9418	likely_pathogenic	0.9494	pathogenic	-0.179	Destabilizing	0.987	D	0.436	neutral	None	None	None	None	N
K/H	0.8146	likely_pathogenic	0.835	pathogenic	-0.227	Destabilizing	0.999	D	0.463	neutral	None	None	None	None	N
K/I	0.916	likely_pathogenic	0.9372	pathogenic	0.085	Stabilizing	0.296	N	0.433	neutral	N	0.485700831	None	None	N
K/L	0.818	likely_pathogenic	0.8603	pathogenic	0.085	Stabilizing	0.001	N	0.26	neutral	None	None	None	None	N
K/M	0.7241	likely_pathogenic	0.7997	pathogenic	-0.244	Destabilizing	0.15	N	0.297	neutral	None	None	None	None	N
K/N	0.9555	likely_pathogenic	0.9698	pathogenic	-0.169	Destabilizing	0.998	D	0.421	neutral	N	0.504837501	None	None	N
K/P	0.9539	likely_pathogenic	0.9622	pathogenic	0.049	Stabilizing	0.999	D	0.458	neutral	None	None	None	None	N
K/Q	0.6145	likely_pathogenic	0.6624	pathogenic	-0.312	Destabilizing	0.961	D	0.415	neutral	N	0.464403344	None	None	N
K/R	0.1351	likely_benign	0.1302	benign	-0.239	Destabilizing	0.915	D	0.409	neutral	N	0.479539198	None	None	N
K/S	0.9597	likely_pathogenic	0.9698	pathogenic	-0.508	Destabilizing	0.987	D	0.417	neutral	None	None	None	None	N
K/T	0.8535	likely_pathogenic	0.8936	pathogenic	-0.431	Destabilizing	0.946	D	0.447	neutral	N	0.464505476	None	None	N
K/V	0.8852	likely_pathogenic	0.91	pathogenic	0.049	Stabilizing	0.233	N	0.365	neutral	None	None	None	None	N
K/W	0.9744	likely_pathogenic	0.9778	pathogenic	-0.579	Destabilizing	1.0	D	0.445	neutral	None	None	None	None	N
K/Y	0.9504	likely_pathogenic	0.9609	pathogenic	-0.244	Destabilizing	0.975	D	0.452	neutral	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.