TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29986	90181;90182;90183	chr2:178552944;178552943;178552942	chr2:179417671;179417670;179417669
N2AB	28345	85258;85259;85260	chr2:178552944;178552943;178552942	chr2:179417671;179417670;179417669
N2A	27418	82477;82478;82479	chr2:178552944;178552943;178552942	chr2:179417671;179417670;179417669
N2B	20921	62986;62987;62988	chr2:178552944;178552943;178552942	chr2:179417671;179417670;179417669
Novex-1	21046	63361;63362;63363	chr2:178552944;178552943;178552942	chr2:179417671;179417670;179417669
Novex-2	21113	63562;63563;63564	chr2:178552944;178552943;178552942	chr2:179417671;179417670;179417669
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: Fn3-106
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.3547
• 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/R	None	None	0.026	N	0.137	0.135	0.278968121808	gnomAD-4.0.0	2.05289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69835E-06	0	0
K/T	rs1382190597	-0.002	0.946	N	0.475	0.35	0.328222422547	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/T	rs1382190597	-0.002	0.946	N	0.475	0.35	0.328222422547	gnomAD-4.0.0	6.84295E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99449E-07	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	0.3259	likely_benign	0.288	benign	0.046	Stabilizing	0.919	D	0.487	neutral	None	None	None	None	N
K/C	0.6431	likely_pathogenic	0.5669	pathogenic	-0.262	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/D	0.4797	ambiguous	0.423	ambiguous	-0.122	Destabilizing	0.851	D	0.471	neutral	None	None	None	None	N
K/E	0.202	likely_benign	0.1745	benign	-0.139	Destabilizing	0.046	N	0.089	neutral	N	0.451005803	None	None	N
K/F	0.7599	likely_pathogenic	0.7068	pathogenic	-0.302	Destabilizing	0.996	D	0.54	neutral	None	None	None	None	N
K/G	0.4129	ambiguous	0.3674	ambiguous	-0.089	Destabilizing	0.959	D	0.471	neutral	None	None	None	None	N
K/H	0.2554	likely_benign	0.223	benign	-0.264	Destabilizing	0.988	D	0.493	neutral	None	None	None	None	N
K/I	0.3834	ambiguous	0.3497	ambiguous	0.316	Stabilizing	0.984	D	0.533	neutral	N	0.479486314	None	None	N
K/L	0.3908	ambiguous	0.357	ambiguous	0.316	Stabilizing	0.919	D	0.447	neutral	None	None	None	None	N
K/M	0.2811	likely_benign	0.2511	benign	0.094	Stabilizing	0.999	D	0.492	neutral	None	None	None	None	N
K/N	0.3427	ambiguous	0.2881	benign	0.231	Stabilizing	0.896	D	0.467	neutral	N	0.418106738	None	None	N
K/P	0.7583	likely_pathogenic	0.7395	pathogenic	0.25	Stabilizing	0.996	D	0.469	neutral	None	None	None	None	N
K/Q	0.1198	likely_benign	0.1101	benign	0.046	Stabilizing	0.896	D	0.5	neutral	N	0.513363771	None	None	N
K/R	0.0848	likely_benign	0.0862	benign	0.039	Stabilizing	0.026	N	0.137	neutral	N	0.497836958	None	None	N
K/S	0.3335	likely_benign	0.2945	benign	-0.186	Destabilizing	0.919	D	0.445	neutral	None	None	None	None	N
K/T	0.1456	likely_benign	0.1348	benign	-0.081	Destabilizing	0.946	D	0.475	neutral	N	0.459259927	None	None	N
K/V	0.344	ambiguous	0.3128	benign	0.25	Stabilizing	0.988	D	0.433	neutral	None	None	None	None	N
K/W	0.8067	likely_pathogenic	0.7718	pathogenic	-0.371	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
K/Y	0.5926	likely_pathogenic	0.5394	ambiguous	-0.007	Destabilizing	0.996	D	0.521	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.