TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22055	66388;66389;66390	chr2:178582206;178582205;178582204	chr2:179446933;179446932;179446931
N2AB	20414	61465;61466;61467	chr2:178582206;178582205;178582204	chr2:179446933;179446932;179446931
N2A	19487	58684;58685;58686	chr2:178582206;178582205;178582204	chr2:179446933;179446932;179446931
N2B	12990	39193;39194;39195	chr2:178582206;178582205;178582204	chr2:179446933;179446932;179446931
Novex-1	13115	39568;39569;39570	chr2:178582206;178582205;178582204	chr2:179446933;179446932;179446931
Novex-2	13182	39769;39770;39771	chr2:178582206;178582205;178582204	chr2:179446933;179446932;179446931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-48
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3737
• 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
P/L	None	None	0.104	N	0.433	0.19	0.380564188046	gnomAD-4.0.0	6.9344E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03386E-07	0	0
P/Q	rs1286811365	-0.017	0.924	N	0.463	0.278	0.359963025489	gnomAD-2.1.1	4.36E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.36E-06	0
P/Q	rs1286811365	-0.017	0.924	N	0.463	0.278	0.359963025489	gnomAD-4.0.0	8.32128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.08406E-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
P/A	0.0887	likely_benign	0.0708	benign	-0.361	Destabilizing	0.104	N	0.327	neutral	N	0.510107248	None	None	N
P/C	0.4239	ambiguous	0.3669	ambiguous	-0.523	Destabilizing	0.953	D	0.512	neutral	None	None	None	None	N
P/D	0.8272	likely_pathogenic	0.7468	pathogenic	-0.074	Destabilizing	0.822	D	0.468	neutral	None	None	None	None	N
P/E	0.4315	ambiguous	0.3514	ambiguous	-0.199	Destabilizing	0.603	D	0.441	neutral	None	None	None	None	N
P/F	0.582	likely_pathogenic	0.465	ambiguous	-0.8	Destabilizing	0.724	D	0.673	prob.neutral	None	None	None	None	N
P/G	0.6071	likely_pathogenic	0.4706	ambiguous	-0.459	Destabilizing	0.603	D	0.371	neutral	None	None	None	None	N
P/H	0.3256	likely_benign	0.2422	benign	-0.158	Destabilizing	0.984	D	0.442	neutral	None	None	None	None	N
P/I	0.11	likely_benign	0.0928	benign	-0.263	Destabilizing	0.05	N	0.408	neutral	None	None	None	None	N
P/K	0.2788	likely_benign	0.2305	benign	-0.063	Destabilizing	0.603	D	0.456	neutral	None	None	None	None	N
P/L	0.0994	likely_benign	0.0816	benign	-0.263	Destabilizing	0.104	N	0.433	neutral	N	0.493425642	None	None	N
P/M	0.2374	likely_benign	0.1939	benign	-0.163	Destabilizing	0.724	D	0.565	neutral	None	None	None	None	N
P/N	0.5537	ambiguous	0.4372	ambiguous	0.156	Stabilizing	0.942	D	0.592	neutral	None	None	None	None	N
P/Q	0.2004	likely_benign	0.1572	benign	-0.13	Destabilizing	0.924	D	0.463	neutral	N	0.48595064	None	None	N
P/R	0.2001	likely_benign	0.1585	benign	0.373	Stabilizing	0.8	D	0.602	neutral	N	0.472655323	None	None	N
P/S	0.2373	likely_benign	0.1675	benign	-0.215	Destabilizing	0.361	N	0.308	neutral	N	0.467592895	None	None	N
P/T	0.0962	likely_benign	0.0704	benign	-0.243	Destabilizing	0.189	N	0.299	neutral	N	0.484936681	None	None	N
P/V	0.082	likely_benign	0.0683	benign	-0.262	Destabilizing	None	N	0.145	neutral	None	None	None	None	N
P/W	0.857	likely_pathogenic	0.7826	pathogenic	-0.857	Destabilizing	0.984	D	0.61	neutral	None	None	None	None	N
P/Y	0.6205	likely_pathogenic	0.4945	ambiguous	-0.499	Destabilizing	0.842	D	0.679	prob.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.