TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30003	90232;90233;90234	chr2:178552893;178552892;178552891	chr2:179417620;179417619;179417618
N2AB	28362	85309;85310;85311	chr2:178552893;178552892;178552891	chr2:179417620;179417619;179417618
N2A	27435	82528;82529;82530	chr2:178552893;178552892;178552891	chr2:179417620;179417619;179417618
N2B	20938	63037;63038;63039	chr2:178552893;178552892;178552891	chr2:179417620;179417619;179417618
Novex-1	21063	63412;63413;63414	chr2:178552893;178552892;178552891	chr2:179417620;179417619;179417618
Novex-2	21130	63613;63614;63615	chr2:178552893;178552892;178552891	chr2:179417620;179417619;179417618
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: Fn3-106
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0834
• 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/L	rs761627535	-1.364	0.055	N	0.724	0.355	0.219573609325	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	2.03063E-04	None	0	0	None	0	None	0	8.9E-06	0
F/L	rs761627535	-1.364	0.055	N	0.724	0.355	0.219573609325	gnomAD-4.0.0	2.0686E-05	None	None	None	None	N	None	0	2.05818E-04	None	0	0	None	0	0	1.14319E-05	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
F/A	0.8993	likely_pathogenic	0.8731	pathogenic	-2.751	Highly Destabilizing	0.272	N	0.832	deleterious	None	None	None	None	N
F/C	0.4762	ambiguous	0.4077	ambiguous	-1.43	Destabilizing	0.958	D	0.88	deleterious	N	0.485254449	None	None	N
F/D	0.9801	likely_pathogenic	0.9781	pathogenic	-3.345	Highly Destabilizing	0.726	D	0.893	deleterious	None	None	None	None	N
F/E	0.9873	likely_pathogenic	0.986	pathogenic	-3.128	Highly Destabilizing	0.726	D	0.885	deleterious	None	None	None	None	N
F/G	0.9602	likely_pathogenic	0.9535	pathogenic	-3.193	Highly Destabilizing	0.726	D	0.86	deleterious	None	None	None	None	N
F/H	0.7813	likely_pathogenic	0.7604	pathogenic	-1.838	Destabilizing	0.567	D	0.83	deleterious	None	None	None	None	N
F/I	0.5085	ambiguous	0.4395	ambiguous	-1.298	Destabilizing	0.22	N	0.763	deleterious	N	0.466225972	None	None	N
F/K	0.9884	likely_pathogenic	0.9868	pathogenic	-1.936	Destabilizing	0.567	D	0.89	deleterious	None	None	None	None	N
F/L	0.9405	likely_pathogenic	0.9241	pathogenic	-1.298	Destabilizing	0.055	N	0.724	prob.delet.	N	0.447293494	None	None	N
F/M	0.8196	likely_pathogenic	0.7801	pathogenic	-0.921	Destabilizing	0.726	D	0.789	deleterious	None	None	None	None	N
F/N	0.8993	likely_pathogenic	0.8896	pathogenic	-2.488	Highly Destabilizing	0.726	D	0.895	deleterious	None	None	None	None	N
F/P	0.9974	likely_pathogenic	0.9969	pathogenic	-1.796	Destabilizing	0.89	D	0.889	deleterious	None	None	None	None	N
F/Q	0.9626	likely_pathogenic	0.9575	pathogenic	-2.409	Highly Destabilizing	0.726	D	0.898	deleterious	None	None	None	None	N
F/R	0.9638	likely_pathogenic	0.96	pathogenic	-1.546	Destabilizing	0.567	D	0.897	deleterious	None	None	None	None	N
F/S	0.7921	likely_pathogenic	0.7525	pathogenic	-3.031	Highly Destabilizing	0.497	N	0.842	deleterious	N	0.485081091	None	None	N
F/T	0.8813	likely_pathogenic	0.8568	pathogenic	-2.702	Highly Destabilizing	0.567	D	0.835	deleterious	None	None	None	None	N
F/V	0.4348	ambiguous	0.372	ambiguous	-1.796	Destabilizing	0.22	N	0.793	deleterious	N	0.455451617	None	None	N
F/W	0.5863	likely_pathogenic	0.5638	ambiguous	-0.353	Destabilizing	0.726	D	0.766	deleterious	None	None	None	None	N
F/Y	0.081	likely_benign	0.0844	benign	-0.747	Destabilizing	None	N	0.424	neutral	N	0.179838987	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.