TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27825	83698;83699;83700	chr2:178562659;178562658;178562657	chr2:179427386;179427385;179427384
N2AB	26184	78775;78776;78777	chr2:178562659;178562658;178562657	chr2:179427386;179427385;179427384
N2A	25257	75994;75995;75996	chr2:178562659;178562658;178562657	chr2:179427386;179427385;179427384
N2B	18760	56503;56504;56505	chr2:178562659;178562658;178562657	chr2:179427386;179427385;179427384
Novex-1	18885	56878;56879;56880	chr2:178562659;178562658;178562657	chr2:179427386;179427385;179427384
Novex-2	18952	57079;57080;57081	chr2:178562659;178562658;178562657	chr2:179427386;179427385;179427384
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-90
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.149
• 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
F/S	None	None	0.815	N	0.565	0.361	0.490976584422	gnomAD-4.0.0	4.89272E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89847E-05	0	0	0	6.17475E-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
F/A	0.6506	likely_pathogenic	0.6868	pathogenic	-2.197	Highly Destabilizing	0.742	D	0.52	neutral	None	None	None	None	N
F/C	0.2534	likely_benign	0.2703	benign	-1.472	Destabilizing	0.994	D	0.623	neutral	N	0.476461608	None	None	N
F/D	0.9547	likely_pathogenic	0.9651	pathogenic	-1.946	Destabilizing	0.984	D	0.643	neutral	None	None	None	None	N
F/E	0.9489	likely_pathogenic	0.9595	pathogenic	-1.761	Destabilizing	0.984	D	0.635	neutral	None	None	None	None	N
F/G	0.8557	likely_pathogenic	0.8776	pathogenic	-2.613	Highly Destabilizing	0.854	D	0.628	neutral	None	None	None	None	N
F/H	0.601	likely_pathogenic	0.6126	pathogenic	-1.002	Destabilizing	0.91	D	0.547	neutral	None	None	None	None	N
F/I	0.3001	likely_benign	0.3461	ambiguous	-0.884	Destabilizing	0.003	N	0.182	neutral	N	0.457182414	None	None	N
F/K	0.9403	likely_pathogenic	0.9522	pathogenic	-1.761	Destabilizing	0.953	D	0.635	neutral	None	None	None	None	N
F/L	0.7646	likely_pathogenic	0.812	pathogenic	-0.884	Destabilizing	0.063	N	0.337	neutral	N	0.483000791	None	None	N
F/M	0.4921	ambiguous	0.5399	ambiguous	-0.669	Destabilizing	0.91	D	0.459	neutral	None	None	None	None	N
F/N	0.8483	likely_pathogenic	0.8592	pathogenic	-2.193	Highly Destabilizing	0.984	D	0.649	neutral	None	None	None	None	N
F/P	0.9964	likely_pathogenic	0.9977	pathogenic	-1.325	Destabilizing	0.984	D	0.675	prob.neutral	None	None	None	None	N
F/Q	0.8634	likely_pathogenic	0.8842	pathogenic	-2.091	Highly Destabilizing	0.984	D	0.676	prob.neutral	None	None	None	None	N
F/R	0.8795	likely_pathogenic	0.9032	pathogenic	-1.342	Destabilizing	0.953	D	0.658	neutral	None	None	None	None	N
F/S	0.5998	likely_pathogenic	0.6336	pathogenic	-2.893	Highly Destabilizing	0.815	D	0.565	neutral	N	0.471257107	None	None	N
F/T	0.6912	likely_pathogenic	0.7171	pathogenic	-2.595	Highly Destabilizing	0.742	D	0.549	neutral	None	None	None	None	N
F/V	0.2682	likely_benign	0.304	benign	-1.325	Destabilizing	0.134	N	0.471	neutral	N	0.474917239	None	None	N
F/W	0.375	ambiguous	0.421	ambiguous	0.003	Stabilizing	0.984	D	0.473	neutral	None	None	None	None	N
F/Y	0.1295	likely_benign	0.1287	benign	-0.32	Destabilizing	0.012	N	0.164	neutral	N	0.396245811	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.