TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16979	51160;51161;51162	chr2:178611194;178611193;178611192	chr2:179475921;179475920;179475919
N2AB	15338	46237;46238;46239	chr2:178611194;178611193;178611192	chr2:179475921;179475920;179475919
N2A	14411	43456;43457;43458	chr2:178611194;178611193;178611192	chr2:179475921;179475920;179475919
N2B	7914	23965;23966;23967	chr2:178611194;178611193;178611192	chr2:179475921;179475920;179475919
Novex-1	8039	24340;24341;24342	chr2:178611194;178611193;178611192	chr2:179475921;179475920;179475919
Novex-2	8106	24541;24542;24543	chr2:178611194;178611193;178611192	chr2:179475921;179475920;179475919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-111
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5698
• Predicted PPI site: I

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
R/G	rs1559776809	None	0.99	N	0.544	0.433	0.506793516358	gnomAD-4.0.0	3.18681E-06	None	None	None	None	I	None	0	0	None	0	5.57693E-05	None	0	0	0	0	0
R/K	None	None	0.4	N	0.164	0.117	0.285698343383	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
R/S	None	None	0.98	N	0.589	0.37	0.314417295294	gnomAD-4.0.0	6.84606E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65832E-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
R/A	0.6217	likely_pathogenic	0.5991	pathogenic	-0.017	Destabilizing	0.985	D	0.573	neutral	None	None	None	None	I
R/C	0.2289	likely_benign	0.2238	benign	-0.079	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
R/D	0.8446	likely_pathogenic	0.8255	pathogenic	-0.011	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	I
R/E	0.545	ambiguous	0.5358	ambiguous	0.058	Stabilizing	0.985	D	0.521	neutral	None	None	None	None	I
R/F	0.7046	likely_pathogenic	0.7054	pathogenic	-0.183	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	I
R/G	0.5334	ambiguous	0.4993	ambiguous	-0.231	Destabilizing	0.99	D	0.544	neutral	N	0.498894099	None	None	I
R/H	0.1118	likely_benign	0.1094	benign	-0.718	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
R/I	0.3886	ambiguous	0.3764	ambiguous	0.515	Stabilizing	0.606	D	0.413	neutral	N	0.510139467	None	None	I
R/K	0.136	likely_benign	0.1411	benign	-0.032	Destabilizing	0.4	N	0.164	neutral	N	0.483335599	None	None	I
R/L	0.3552	ambiguous	0.3427	ambiguous	0.515	Stabilizing	0.971	D	0.559	neutral	None	None	None	None	I
R/M	0.404	ambiguous	0.392	ambiguous	0.104	Stabilizing	0.998	D	0.605	neutral	None	None	None	None	I
R/N	0.7163	likely_pathogenic	0.7079	pathogenic	0.274	Stabilizing	0.998	D	0.537	neutral	None	None	None	None	I
R/P	0.9498	likely_pathogenic	0.9394	pathogenic	0.359	Stabilizing	0.999	D	0.642	neutral	None	None	None	None	I
R/Q	0.1337	likely_benign	0.1298	benign	0.147	Stabilizing	0.996	D	0.582	neutral	None	None	None	None	I
R/S	0.6386	likely_pathogenic	0.6161	pathogenic	-0.126	Destabilizing	0.98	D	0.589	neutral	N	0.489412855	None	None	I
R/T	0.3417	ambiguous	0.3209	benign	0.084	Stabilizing	0.99	D	0.572	neutral	N	0.487524179	None	None	I
R/V	0.4749	ambiguous	0.4614	ambiguous	0.359	Stabilizing	0.971	D	0.559	neutral	None	None	None	None	I
R/W	0.2655	likely_benign	0.2619	benign	-0.187	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
R/Y	0.5321	ambiguous	0.5323	ambiguous	0.214	Stabilizing	0.999	D	0.637	neutral	None	None	None	None	I

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.