TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14106	42541;42542;42543	chr2:178634465;178634464;178634463	chr2:179499192;179499191;179499190
N2AB	12465	37618;37619;37620	chr2:178634465;178634464;178634463	chr2:179499192;179499191;179499190
N2A	11538	34837;34838;34839	chr2:178634465;178634464;178634463	chr2:179499192;179499191;179499190
N2B	5041	15346;15347;15348	chr2:178634465;178634464;178634463	chr2:179499192;179499191;179499190
Novex-1	5166	15721;15722;15723	chr2:178634465;178634464;178634463	chr2:179499192;179499191;179499190
Novex-2	5233	15922;15923;15924	chr2:178634465;178634464;178634463	chr2:179499192;179499191;179499190
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: Ig-91
• Domain position: 53
• Structural Position: 135
• Q(SASA): 0.4208
• 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	0.998	N	0.511	0.232	0.403896168776	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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	0.9339	likely_pathogenic	0.9	pathogenic	-0.604	Destabilizing	0.996	D	0.586	neutral	None	None	None	None	N
K/C	0.9588	likely_pathogenic	0.9277	pathogenic	-0.601	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/D	0.9709	likely_pathogenic	0.9523	pathogenic	-0.803	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/E	0.8166	likely_pathogenic	0.6922	pathogenic	-0.666	Destabilizing	0.998	D	0.511	neutral	D	0.573258845	None	None	N
K/F	0.985	likely_pathogenic	0.9735	pathogenic	-0.112	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
K/G	0.9534	likely_pathogenic	0.9312	pathogenic	-1.018	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/H	0.731	likely_pathogenic	0.6142	pathogenic	-1.498	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/I	0.8268	likely_pathogenic	0.7484	pathogenic	0.494	Stabilizing	0.733	D	0.534	neutral	N	0.509067921	None	None	N
K/L	0.8584	likely_pathogenic	0.7822	pathogenic	0.494	Stabilizing	0.983	D	0.577	neutral	None	None	None	None	N
K/M	0.7422	likely_pathogenic	0.6226	pathogenic	0.437	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/N	0.8831	likely_pathogenic	0.8086	pathogenic	-0.938	Destabilizing	0.999	D	0.691	prob.neutral	D	0.541988563	None	None	N
K/P	0.9936	likely_pathogenic	0.9917	pathogenic	0.158	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/Q	0.5425	ambiguous	0.3953	ambiguous	-0.917	Destabilizing	0.999	D	0.7	prob.neutral	D	0.536340019	None	None	N
K/R	0.1687	likely_benign	0.1397	benign	-1.093	Destabilizing	0.998	D	0.511	neutral	N	0.496827682	None	None	N
K/S	0.9354	likely_pathogenic	0.885	pathogenic	-1.43	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
K/T	0.641	likely_pathogenic	0.5439	ambiguous	-1.087	Destabilizing	0.998	D	0.731	prob.delet.	N	0.508164819	None	None	N
K/V	0.8053	likely_pathogenic	0.7413	pathogenic	0.158	Stabilizing	0.983	D	0.59	neutral	None	None	None	None	N
K/W	0.9764	likely_pathogenic	0.9572	pathogenic	-0.098	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/Y	0.9324	likely_pathogenic	0.8977	pathogenic	0.196	Stabilizing	1.0	D	0.769	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.