TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7906	23941;23942;23943	chr2:178719776;178719775;178719774	chr2:179584503;179584502;179584501
N2AB	7589	22990;22991;22992	chr2:178719776;178719775;178719774	chr2:179584503;179584502;179584501
N2A	6662	20209;20210;20211	chr2:178719776;178719775;178719774	chr2:179584503;179584502;179584501
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-64
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2114
• 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	rs753446112	-1.133	0.002	N	0.185	0.201	0.0920862733494	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	1.11421E-04	None	0	None	0	0	0
F/L	rs753446112	-1.133	0.002	N	0.185	0.201	0.0920862733494	gnomAD-4.0.0	1.91094E-05	None	None	None	None	N	None	0	0	None	0	3.32853E-04	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
F/A	0.7473	likely_pathogenic	0.7118	pathogenic	-3.031	Highly Destabilizing	0.004	N	0.349	neutral	None	None	None	None	N
F/C	0.4154	ambiguous	0.3862	ambiguous	-2.107	Highly Destabilizing	0.006	N	0.397	neutral	N	0.41463121	None	None	N
F/D	0.9919	likely_pathogenic	0.991	pathogenic	-3.79	Highly Destabilizing	0.944	D	0.734	prob.delet.	None	None	None	None	N
F/E	0.9909	likely_pathogenic	0.9907	pathogenic	-3.59	Highly Destabilizing	0.828	D	0.709	prob.delet.	None	None	None	None	N
F/G	0.9549	likely_pathogenic	0.9422	pathogenic	-3.462	Highly Destabilizing	0.704	D	0.601	neutral	None	None	None	None	N
F/H	0.9439	likely_pathogenic	0.9467	pathogenic	-1.983	Destabilizing	0.981	D	0.635	neutral	None	None	None	None	N
F/I	0.2712	likely_benign	0.2514	benign	-1.613	Destabilizing	0.27	N	0.499	neutral	N	0.38751918	None	None	N
F/K	0.9909	likely_pathogenic	0.9912	pathogenic	-2.632	Highly Destabilizing	0.828	D	0.7	prob.neutral	None	None	None	None	N
F/L	0.8534	likely_pathogenic	0.8371	pathogenic	-1.613	Destabilizing	0.002	N	0.185	neutral	N	0.391788849	None	None	N
F/M	0.626	likely_pathogenic	0.6037	pathogenic	-1.227	Destabilizing	0.893	D	0.602	neutral	None	None	None	None	N
F/N	0.9741	likely_pathogenic	0.9716	pathogenic	-3.173	Highly Destabilizing	0.981	D	0.714	prob.delet.	None	None	None	None	N
F/P	0.9962	likely_pathogenic	0.9956	pathogenic	-2.099	Highly Destabilizing	0.944	D	0.721	prob.delet.	None	None	None	None	N
F/Q	0.98	likely_pathogenic	0.9808	pathogenic	-3.14	Highly Destabilizing	0.981	D	0.707	prob.neutral	None	None	None	None	N
F/R	0.9745	likely_pathogenic	0.976	pathogenic	-2.051	Highly Destabilizing	0.944	D	0.721	prob.delet.	None	None	None	None	N
F/S	0.8439	likely_pathogenic	0.8234	pathogenic	-3.731	Highly Destabilizing	0.473	N	0.561	neutral	N	0.49230256	None	None	N
F/T	0.8473	likely_pathogenic	0.8298	pathogenic	-3.42	Highly Destabilizing	0.704	D	0.577	neutral	None	None	None	None	N
F/V	0.2477	likely_benign	0.2319	benign	-2.099	Highly Destabilizing	0.01	N	0.301	neutral	N	0.353710463	None	None	N
F/W	0.8189	likely_pathogenic	0.813	pathogenic	-0.735	Destabilizing	0.995	D	0.581	neutral	None	None	None	None	N
F/Y	0.4195	ambiguous	0.4261	ambiguous	-1.122	Destabilizing	0.917	D	0.565	neutral	N	0.469250465	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.