TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27637	83134;83135;83136	chr2:178563223;178563222;178563221	chr2:179427950;179427949;179427948
N2AB	25996	78211;78212;78213	chr2:178563223;178563222;178563221	chr2:179427950;179427949;179427948
N2A	25069	75430;75431;75432	chr2:178563223;178563222;178563221	chr2:179427950;179427949;179427948
N2B	18572	55939;55940;55941	chr2:178563223;178563222;178563221	chr2:179427950;179427949;179427948
Novex-1	18697	56314;56315;56316	chr2:178563223;178563222;178563221	chr2:179427950;179427949;179427948
Novex-2	18764	56515;56516;56517	chr2:178563223;178563222;178563221	chr2:179427950;179427949;179427948
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: Fn3-89
• Domain position: 68
• Structural Position: 98
• Q(SASA): 0.6374
• 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	rs755617634	-0.173	0.935	N	0.437	0.258	0.158396225186	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	0	None	0	3.07692E-04	None	0	None	0	0	0
K/N	rs755617634	-0.173	0.935	N	0.437	0.258	0.158396225186	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93274E-04	None	0	0	0	0	0
K/N	rs755617634	-0.173	0.935	N	0.437	0.258	0.158396225186	gnomAD-4.0.0	5.12483E-06	None	None	None	None	N	None	0	0	None	0	9.70026E-05	None	0	0	0	0	0
K/T	None	None	0.967	N	0.449	0.517	0.347659731818	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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	0.2504	likely_benign	0.2493	benign	-0.403	Destabilizing	0.916	D	0.483	neutral	None	None	None	None	N
K/C	0.5836	likely_pathogenic	0.6285	pathogenic	-0.572	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
K/D	0.5069	ambiguous	0.4767	ambiguous	0.058	Stabilizing	0.033	N	0.349	neutral	None	None	None	None	N
K/E	0.1356	likely_benign	0.1217	benign	0.13	Stabilizing	0.805	D	0.473	neutral	N	0.497970244	None	None	N
K/F	0.6952	likely_pathogenic	0.7045	pathogenic	-0.412	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
K/G	0.4073	ambiguous	0.3945	ambiguous	-0.671	Destabilizing	0.916	D	0.478	neutral	None	None	None	None	N
K/H	0.2634	likely_benign	0.2785	benign	-0.85	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
K/I	0.2349	likely_benign	0.2342	benign	0.252	Stabilizing	0.983	D	0.661	neutral	N	0.450296514	None	None	N
K/L	0.2388	likely_benign	0.2268	benign	0.252	Stabilizing	0.987	D	0.456	neutral	None	None	None	None	N
K/M	0.1736	likely_benign	0.162	benign	-0.054	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	N
K/N	0.361	ambiguous	0.3381	benign	-0.262	Destabilizing	0.935	D	0.437	neutral	N	0.475538888	None	None	N
K/P	0.5894	likely_pathogenic	0.5651	pathogenic	0.062	Stabilizing	0.987	D	0.537	neutral	None	None	None	None	N
K/Q	0.1019	likely_benign	0.1035	benign	-0.307	Destabilizing	0.967	D	0.464	neutral	N	0.482579504	None	None	N
K/R	0.0777	likely_benign	0.0804	benign	-0.267	Destabilizing	0.056	N	0.319	neutral	N	0.45190988	None	None	N
K/S	0.3347	likely_benign	0.3255	benign	-0.827	Destabilizing	0.916	D	0.476	neutral	None	None	None	None	N
K/T	0.1251	likely_benign	0.1216	benign	-0.567	Destabilizing	0.967	D	0.449	neutral	N	0.449275007	None	None	N
K/V	0.2159	likely_benign	0.2181	benign	0.062	Stabilizing	0.987	D	0.595	neutral	None	None	None	None	N
K/W	0.6626	likely_pathogenic	0.6905	pathogenic	-0.38	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/Y	0.6037	likely_pathogenic	0.6105	pathogenic	-0.06	Destabilizing	0.996	D	0.616	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.