TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19277	58054;58055;58056	chr2:178595525;178595524;178595523	chr2:179460252;179460251;179460250
N2AB	17636	53131;53132;53133	chr2:178595525;178595524;178595523	chr2:179460252;179460251;179460250
N2A	16709	50350;50351;50352	chr2:178595525;178595524;178595523	chr2:179460252;179460251;179460250
N2B	10212	30859;30860;30861	chr2:178595525;178595524;178595523	chr2:179460252;179460251;179460250
Novex-1	10337	31234;31235;31236	chr2:178595525;178595524;178595523	chr2:179460252;179460251;179460250
Novex-2	10404	31435;31436;31437	chr2:178595525;178595524;178595523	chr2:179460252;179460251;179460250
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-27
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.384
• 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
V/I	rs1398372843	-0.044	None	N	0.114	0.075	0.422160833541	gnomAD-2.1.1	5.91E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.47E-05	0
V/I	rs1398372843	-0.044	None	N	0.114	0.075	0.422160833541	gnomAD-4.0.0	7.11096E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.23996E-07	0	0
V/L	None	None	None	N	0.103	0.072	0.347879110917	gnomAD-4.0.0	7.11096E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.23996E-07	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
V/A	0.209	likely_benign	0.2479	benign	-0.879	Destabilizing	0.025	N	0.427	neutral	N	0.521375539	None	None	N
V/C	0.6537	likely_pathogenic	0.7003	pathogenic	-0.809	Destabilizing	0.869	D	0.528	neutral	None	None	None	None	N
V/D	0.3211	likely_benign	0.427	ambiguous	-0.341	Destabilizing	0.303	N	0.684	prob.delet.	N	0.502262874	None	None	N
V/E	0.2475	likely_benign	0.3203	benign	-0.361	Destabilizing	0.366	N	0.617	neutral	None	None	None	None	N
V/F	0.1663	likely_benign	0.1964	benign	-0.605	Destabilizing	0.177	N	0.597	neutral	D	0.533286044	None	None	N
V/G	0.2809	likely_benign	0.3336	benign	-1.145	Destabilizing	0.303	N	0.655	prob.neutral	N	0.501755895	None	None	N
V/H	0.4565	ambiguous	0.5519	ambiguous	-0.523	Destabilizing	0.869	D	0.674	prob.neutral	None	None	None	None	N
V/I	0.0713	likely_benign	0.0737	benign	-0.277	Destabilizing	None	N	0.114	neutral	N	0.491572707	None	None	N
V/K	0.3472	ambiguous	0.4393	ambiguous	-0.762	Destabilizing	0.366	N	0.602	neutral	None	None	None	None	N
V/L	0.1093	likely_benign	0.1323	benign	-0.277	Destabilizing	None	N	0.103	neutral	N	0.463655387	None	None	N
V/M	0.1307	likely_benign	0.1451	benign	-0.403	Destabilizing	0.221	N	0.537	neutral	None	None	None	None	N
V/N	0.2285	likely_benign	0.2816	benign	-0.623	Destabilizing	0.366	N	0.717	prob.delet.	None	None	None	None	N
V/P	0.4376	ambiguous	0.4771	ambiguous	-0.441	Destabilizing	0.637	D	0.665	prob.neutral	None	None	None	None	N
V/Q	0.2936	likely_benign	0.3454	ambiguous	-0.746	Destabilizing	0.637	D	0.629	neutral	None	None	None	None	N
V/R	0.3364	likely_benign	0.4245	ambiguous	-0.294	Destabilizing	0.366	N	0.715	prob.delet.	None	None	None	None	N
V/S	0.234	likely_benign	0.274	benign	-1.147	Destabilizing	0.039	N	0.598	neutral	None	None	None	None	N
V/T	0.1575	likely_benign	0.1805	benign	-1.046	Destabilizing	0.001	N	0.257	neutral	None	None	None	None	N
V/W	0.7518	likely_pathogenic	0.8176	pathogenic	-0.743	Destabilizing	0.869	D	0.715	prob.delet.	None	None	None	None	N
V/Y	0.4691	ambiguous	0.5484	ambiguous	-0.445	Destabilizing	0.366	N	0.602	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.