TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27449	82570;82571;82572	chr2:178563787;178563786;178563785	chr2:179428514;179428513;179428512
N2AB	25808	77647;77648;77649	chr2:178563787;178563786;178563785	chr2:179428514;179428513;179428512
N2A	24881	74866;74867;74868	chr2:178563787;178563786;178563785	chr2:179428514;179428513;179428512
N2B	18384	55375;55376;55377	chr2:178563787;178563786;178563785	chr2:179428514;179428513;179428512
Novex-1	18509	55750;55751;55752	chr2:178563787;178563786;178563785	chr2:179428514;179428513;179428512
Novex-2	18576	55951;55952;55953	chr2:178563787;178563786;178563785	chr2:179428514;179428513;179428512
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: Fn3-87
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.555
• 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
K/I	rs750788494	0.44	0.983	N	0.647	0.423	0.466740653422	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/Q	rs925851202	None	0.935	N	0.471	0.299	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.77555E-04
K/Q	rs925851202	None	0.935	N	0.471	0.299	None	gnomAD-4.0.0	6.57488E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	4.77555E-04

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	0.5404	ambiguous	0.5952	pathogenic	-0.158	Destabilizing	0.845	D	0.57	neutral	None	None	None	None	I
K/C	0.79	likely_pathogenic	0.8221	pathogenic	-0.411	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
K/D	0.7622	likely_pathogenic	0.7694	pathogenic	0.074	Stabilizing	0.845	D	0.587	neutral	None	None	None	None	I
K/E	0.3633	ambiguous	0.4055	ambiguous	0.094	Stabilizing	0.025	N	0.372	neutral	N	0.503453421	None	None	I
K/F	0.9183	likely_pathogenic	0.9253	pathogenic	-0.388	Destabilizing	0.987	D	0.651	neutral	None	None	None	None	I
K/G	0.7245	likely_pathogenic	0.7431	pathogenic	-0.351	Destabilizing	0.845	D	0.582	neutral	None	None	None	None	I
K/H	0.4239	ambiguous	0.4471	ambiguous	-0.573	Destabilizing	0.997	D	0.524	neutral	None	None	None	None	I
K/I	0.5055	ambiguous	0.5604	ambiguous	0.274	Stabilizing	0.983	D	0.647	neutral	N	0.468027876	None	None	I
K/L	0.5766	likely_pathogenic	0.6109	pathogenic	0.274	Stabilizing	0.975	D	0.527	neutral	None	None	None	None	I
K/M	0.4059	ambiguous	0.4416	ambiguous	-0.012	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	I
K/N	0.6498	likely_pathogenic	0.6763	pathogenic	0.032	Stabilizing	0.967	D	0.483	neutral	N	0.474811825	None	None	I
K/P	0.7854	likely_pathogenic	0.7801	pathogenic	0.157	Stabilizing	0.987	D	0.539	neutral	None	None	None	None	I
K/Q	0.2062	likely_benign	0.2321	benign	-0.084	Destabilizing	0.935	D	0.471	neutral	N	0.472013894	None	None	I
K/R	0.0912	likely_benign	0.0974	benign	-0.102	Destabilizing	0.892	D	0.471	neutral	D	0.523636692	None	None	I
K/S	0.6026	likely_pathogenic	0.6405	pathogenic	-0.458	Destabilizing	0.128	N	0.413	neutral	None	None	None	None	I
K/T	0.3129	likely_benign	0.3653	ambiguous	-0.282	Destabilizing	0.805	D	0.559	neutral	N	0.47339302	None	None	I
K/V	0.5057	ambiguous	0.553	ambiguous	0.157	Stabilizing	0.975	D	0.539	neutral	None	None	None	None	I
K/W	0.8914	likely_pathogenic	0.9037	pathogenic	-0.413	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
K/Y	0.7903	likely_pathogenic	0.8006	pathogenic	-0.062	Destabilizing	0.996	D	0.627	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.