TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26075	78448;78449;78450	chr2:178567909;178567908;178567907	chr2:179432636;179432635;179432634
N2AB	24434	73525;73526;73527	chr2:178567909;178567908;178567907	chr2:179432636;179432635;179432634
N2A	23507	70744;70745;70746	chr2:178567909;178567908;178567907	chr2:179432636;179432635;179432634
N2B	17010	51253;51254;51255	chr2:178567909;178567908;178567907	chr2:179432636;179432635;179432634
Novex-1	17135	51628;51629;51630	chr2:178567909;178567908;178567907	chr2:179432636;179432635;179432634
Novex-2	17202	51829;51830;51831	chr2:178567909;178567908;178567907	chr2:179432636;179432635;179432634
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: Fn3-77
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5372
• 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	rs776380915	0.521	0.991	N	0.729	0.419	0.482646159919	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
K/I	rs776380915	0.521	0.991	N	0.729	0.419	0.482646159919	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs776380915	0.521	0.991	N	0.729	0.419	0.482646159919	gnomAD-4.0.0	6.57592E-06	None	None	None	None	I	None	2.41348E-05	0	None	0	0	None	0	0	0	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	0.4551	ambiguous	0.5811	pathogenic	-0.115	Destabilizing	0.953	D	0.583	neutral	None	None	None	None	I
K/C	0.7709	likely_pathogenic	0.8406	pathogenic	-0.275	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
K/D	0.792	likely_pathogenic	0.856	pathogenic	0.171	Stabilizing	0.986	D	0.587	neutral	None	None	None	None	I
K/E	0.3499	ambiguous	0.465	ambiguous	0.196	Stabilizing	0.885	D	0.573	neutral	N	0.425549998	None	None	I
K/F	0.8724	likely_pathogenic	0.9181	pathogenic	-0.222	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
K/G	0.6526	likely_pathogenic	0.7488	pathogenic	-0.343	Destabilizing	0.953	D	0.574	neutral	None	None	None	None	I
K/H	0.4459	ambiguous	0.523	ambiguous	-0.595	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
K/I	0.5149	ambiguous	0.64	pathogenic	0.414	Stabilizing	0.991	D	0.729	prob.delet.	N	0.484157122	None	None	I
K/L	0.5082	ambiguous	0.6209	pathogenic	0.414	Stabilizing	0.953	D	0.574	neutral	None	None	None	None	I
K/M	0.4189	ambiguous	0.5225	ambiguous	0.185	Stabilizing	0.998	D	0.614	neutral	None	None	None	None	I
K/N	0.6473	likely_pathogenic	0.744	pathogenic	0.167	Stabilizing	0.982	D	0.596	neutral	N	0.480180649	None	None	I
K/P	0.5152	ambiguous	0.6259	pathogenic	0.267	Stabilizing	0.993	D	0.631	neutral	None	None	None	None	I
K/Q	0.2172	likely_benign	0.2756	benign	0.007	Stabilizing	0.322	N	0.337	neutral	N	0.500933191	None	None	I
K/R	0.0859	likely_benign	0.0904	benign	-0.088	Destabilizing	0.046	N	0.341	neutral	N	0.489889478	None	None	I
K/S	0.6157	likely_pathogenic	0.7315	pathogenic	-0.381	Destabilizing	0.953	D	0.6	neutral	None	None	None	None	I
K/T	0.3555	ambiguous	0.4783	ambiguous	-0.195	Destabilizing	0.982	D	0.583	neutral	N	0.518422874	None	None	I
K/V	0.4532	ambiguous	0.5769	pathogenic	0.267	Stabilizing	0.993	D	0.619	neutral	None	None	None	None	I
K/W	0.8758	likely_pathogenic	0.9116	pathogenic	-0.192	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
K/Y	0.7832	likely_pathogenic	0.8441	pathogenic	0.141	Stabilizing	0.998	D	0.709	prob.delet.	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.