TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2223	6892;6893;6894	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769
N2AB	2223	6892;6893;6894	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769
N2A	2223	6892;6893;6894	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769
N2B	2177	6754;6755;6756	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769
Novex-1	2177	6754;6755;6756	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769
Novex-2	2177	6754;6755;6756	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769
Novex-3	2223	6892;6893;6894	chr2:178775044;178775043;178775042	chr2:179639771;179639770;179639769

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-11
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3535
• 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
H/L	rs372979075	0.777	0.008	N	0.424	0.372	0.51098835382	gnomAD-2.1.1	6.72E-05	None	None	None	None	N	None	0	0	None	0	6.53201E-04	None	1.96002E-04	None	0	0	0
H/L	rs372979075	0.777	0.008	N	0.424	0.372	0.51098835382	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	0	0	0	1.15518E-03	None	0	0	0	2.07297E-04	4.78011E-04
H/L	rs372979075	0.777	0.008	N	0.424	0.372	0.51098835382	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	2E-03	0	None	None	None	0	None
H/L	rs372979075	0.777	0.008	N	0.424	0.372	0.51098835382	gnomAD-4.0.0	2.35436E-05	None	None	None	None	N	None	0	1.66639E-05	None	0	4.4607E-04	None	0	0	0	1.53714E-04	4.79954E-05
H/Q	rs1237315602	0.253	0.983	N	0.56	0.242	0.345632371893	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
H/Q	rs1237315602	0.253	0.983	N	0.56	0.242	0.345632371893	gnomAD-4.0.0	1.59082E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
H/R	None	None	0.949	N	0.523	0.384	0.285698343383	gnomAD-4.0.0	6.84121E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99327E-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
H/A	0.8024	likely_pathogenic	0.8093	pathogenic	-0.43	Destabilizing	0.775	D	0.574	neutral	None	None	None	None	N
H/C	0.6325	likely_pathogenic	0.6407	pathogenic	0.295	Stabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
H/D	0.8273	likely_pathogenic	0.8404	pathogenic	-0.366	Destabilizing	0.983	D	0.613	neutral	N	0.50747374	None	None	N
H/E	0.847	likely_pathogenic	0.8556	pathogenic	-0.274	Destabilizing	0.875	D	0.493	neutral	None	None	None	None	N
H/F	0.55	ambiguous	0.5587	ambiguous	0.763	Stabilizing	0.858	D	0.671	neutral	None	None	None	None	N
H/G	0.8562	likely_pathogenic	0.8611	pathogenic	-0.793	Destabilizing	0.875	D	0.616	neutral	None	None	None	None	N
H/I	0.6814	likely_pathogenic	0.698	pathogenic	0.559	Stabilizing	0.858	D	0.645	neutral	None	None	None	None	N
H/K	0.6759	likely_pathogenic	0.6881	pathogenic	-0.257	Destabilizing	0.961	D	0.603	neutral	None	None	None	None	N
H/L	0.3349	likely_benign	0.3441	ambiguous	0.559	Stabilizing	0.008	N	0.424	neutral	N	0.464931474	None	None	N
H/M	0.812	likely_pathogenic	0.8213	pathogenic	0.336	Stabilizing	0.923	D	0.737	prob.delet.	None	None	None	None	N
H/N	0.3989	ambiguous	0.4105	ambiguous	-0.417	Destabilizing	0.941	D	0.507	neutral	N	0.508722194	None	None	N
H/P	0.8829	likely_pathogenic	0.8894	pathogenic	0.252	Stabilizing	0.983	D	0.745	deleterious	D	0.569959842	None	None	N
H/Q	0.5847	likely_pathogenic	0.5923	pathogenic	-0.195	Destabilizing	0.983	D	0.56	neutral	N	0.471231394	None	None	N
H/R	0.3536	ambiguous	0.3641	ambiguous	-0.82	Destabilizing	0.949	D	0.523	neutral	N	0.48743314	None	None	N
H/S	0.7174	likely_pathogenic	0.726	pathogenic	-0.388	Destabilizing	0.875	D	0.569	neutral	None	None	None	None	N
H/T	0.7771	likely_pathogenic	0.7887	pathogenic	-0.186	Destabilizing	0.923	D	0.641	neutral	None	None	None	None	N
H/V	0.6249	likely_pathogenic	0.6428	pathogenic	0.252	Stabilizing	0.633	D	0.612	neutral	None	None	None	None	N
H/W	0.7349	likely_pathogenic	0.7499	pathogenic	1.023	Stabilizing	0.996	D	0.747	deleterious	None	None	None	None	N
H/Y	0.2418	likely_benign	0.2482	benign	1.12	Stabilizing	0.84	D	0.475	neutral	N	0.504722144	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.