TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27378	82357;82358;82359	chr2:178564000;178563999;178563998	chr2:179428727;179428726;179428725
N2AB	25737	77434;77435;77436	chr2:178564000;178563999;178563998	chr2:179428727;179428726;179428725
N2A	24810	74653;74654;74655	chr2:178564000;178563999;178563998	chr2:179428727;179428726;179428725
N2B	18313	55162;55163;55164	chr2:178564000;178563999;178563998	chr2:179428727;179428726;179428725
Novex-1	18438	55537;55538;55539	chr2:178564000;178563999;178563998	chr2:179428727;179428726;179428725
Novex-2	18505	55738;55739;55740	chr2:178564000;178563999;178563998	chr2:179428727;179428726;179428725
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: 10
• Structural Position: 11
• Q(SASA): 0.4961
• 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/T	rs886055240	-0.315	0.549	N	0.504	0.089	0.280987212366	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/T	rs886055240	-0.315	0.549	N	0.504	0.089	0.280987212366	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs886055240	-0.315	0.549	N	0.504	0.089	0.280987212366	gnomAD-4.0.0	4.33821E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08587E-06	0	1.60123E-05

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	0.1651	likely_benign	0.1826	benign	-0.177	Destabilizing	0.4	N	0.499	neutral	None	None	None	None	N
K/C	0.4093	ambiguous	0.4349	ambiguous	-0.355	Destabilizing	0.992	D	0.643	neutral	None	None	None	None	N
K/D	0.3298	likely_benign	0.3581	ambiguous	0.078	Stabilizing	0.447	N	0.508	neutral	None	None	None	None	N
K/E	0.1005	likely_benign	0.1086	benign	0.137	Stabilizing	0.002	N	0.241	neutral	N	0.468380842	None	None	N
K/F	0.4933	ambiguous	0.5352	ambiguous	-0.095	Destabilizing	0.972	D	0.604	neutral	None	None	None	None	N
K/G	0.3114	likely_benign	0.3471	ambiguous	-0.465	Destabilizing	0.447	N	0.566	neutral	None	None	None	None	N
K/H	0.1608	likely_benign	0.17	benign	-0.759	Destabilizing	0.92	D	0.573	neutral	None	None	None	None	N
K/I	0.1562	likely_benign	0.1679	benign	0.527	Stabilizing	0.896	D	0.611	neutral	N	0.513057126	None	None	N
K/L	0.1598	likely_benign	0.1672	benign	0.527	Stabilizing	0.617	D	0.571	neutral	None	None	None	None	N
K/M	0.1238	likely_benign	0.1254	benign	0.228	Stabilizing	0.992	D	0.563	neutral	None	None	None	None	N
K/N	0.2044	likely_benign	0.2281	benign	-0.095	Destabilizing	0.004	N	0.353	neutral	N	0.492508496	None	None	N
K/P	0.7224	likely_pathogenic	0.736	pathogenic	0.323	Stabilizing	0.92	D	0.597	neutral	None	None	None	None	N
K/Q	0.086	likely_benign	0.0897	benign	-0.188	Destabilizing	0.379	N	0.525	neutral	N	0.45583562	None	None	N
K/R	0.0767	likely_benign	0.0774	benign	-0.331	Destabilizing	0.004	N	0.325	neutral	N	0.443002395	None	None	N
K/S	0.2052	likely_benign	0.2283	benign	-0.634	Destabilizing	0.447	N	0.504	neutral	None	None	None	None	N
K/T	0.0881	likely_benign	0.0937	benign	-0.396	Destabilizing	0.549	D	0.504	neutral	N	0.451563163	None	None	N
K/V	0.1397	likely_benign	0.1478	benign	0.323	Stabilizing	0.85	D	0.6	neutral	None	None	None	None	N
K/W	0.5402	ambiguous	0.5828	pathogenic	-0.056	Destabilizing	0.992	D	0.675	prob.neutral	None	None	None	None	N
K/Y	0.3868	ambiguous	0.4147	ambiguous	0.26	Stabilizing	0.972	D	0.596	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.