TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27522	82789;82790;82791	chr2:178563568;178563567;178563566	chr2:179428295;179428294;179428293
N2AB	25881	77866;77867;77868	chr2:178563568;178563567;178563566	chr2:179428295;179428294;179428293
N2A	24954	75085;75086;75087	chr2:178563568;178563567;178563566	chr2:179428295;179428294;179428293
N2B	18457	55594;55595;55596	chr2:178563568;178563567;178563566	chr2:179428295;179428294;179428293
Novex-1	18582	55969;55970;55971	chr2:178563568;178563567;178563566	chr2:179428295;179428294;179428293
Novex-2	18649	56170;56171;56172	chr2:178563568;178563567;178563566	chr2:179428295;179428294;179428293
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: Fn3-88
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.5221
• 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	0.967	N	0.582	0.237	0.178374595973	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.5517	ambiguous	0.5305	ambiguous	0.016	Stabilizing	0.845	D	0.522	neutral	None	None	None	None	N
K/C	0.7823	likely_pathogenic	0.7653	pathogenic	-0.403	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/D	0.7204	likely_pathogenic	0.6898	pathogenic	-0.32	Destabilizing	0.975	D	0.568	neutral	None	None	None	None	N
K/E	0.4096	ambiguous	0.3647	ambiguous	-0.34	Destabilizing	0.892	D	0.501	neutral	N	0.478480406	None	None	N
K/F	0.8847	likely_pathogenic	0.8733	pathogenic	-0.355	Destabilizing	0.987	D	0.652	neutral	None	None	None	None	N
K/G	0.5647	likely_pathogenic	0.5633	ambiguous	-0.094	Destabilizing	0.975	D	0.523	neutral	None	None	None	None	N
K/H	0.3771	ambiguous	0.3656	ambiguous	-0.198	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
K/I	0.6068	likely_pathogenic	0.5613	ambiguous	0.222	Stabilizing	0.967	D	0.639	neutral	N	0.500954621	None	None	N
K/L	0.5898	likely_pathogenic	0.5574	ambiguous	0.222	Stabilizing	0.845	D	0.504	neutral	None	None	None	None	N
K/M	0.4271	ambiguous	0.3952	ambiguous	-0.118	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
K/N	0.5404	ambiguous	0.5103	ambiguous	0.065	Stabilizing	0.967	D	0.582	neutral	N	0.48329158	None	None	N
K/P	0.8706	likely_pathogenic	0.8793	pathogenic	0.175	Stabilizing	0.987	D	0.585	neutral	None	None	None	None	N
K/Q	0.2058	likely_benign	0.1924	benign	-0.084	Destabilizing	0.983	D	0.589	neutral	N	0.457067771	None	None	N
K/R	0.0771	likely_benign	0.076	benign	-0.103	Destabilizing	0.892	D	0.501	neutral	N	0.430227886	None	None	N
K/S	0.6279	likely_pathogenic	0.6086	pathogenic	-0.279	Destabilizing	0.845	D	0.5	neutral	None	None	None	None	N
K/T	0.35	ambiguous	0.3158	benign	-0.193	Destabilizing	0.025	N	0.335	neutral	N	0.449563008	None	None	N
K/V	0.5346	ambiguous	0.4917	ambiguous	0.175	Stabilizing	0.95	D	0.519	neutral	None	None	None	None	N
K/W	0.8354	likely_pathogenic	0.8378	pathogenic	-0.471	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.7225	likely_pathogenic	0.6935	pathogenic	-0.121	Destabilizing	0.996	D	0.603	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.