TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24050	72373;72374;72375	chr2:178573984;178573983;178573982	chr2:179438711;179438710;179438709
N2AB	22409	67450;67451;67452	chr2:178573984;178573983;178573982	chr2:179438711;179438710;179438709
N2A	21482	64669;64670;64671	chr2:178573984;178573983;178573982	chr2:179438711;179438710;179438709
N2B	14985	45178;45179;45180	chr2:178573984;178573983;178573982	chr2:179438711;179438710;179438709
Novex-1	15110	45553;45554;45555	chr2:178573984;178573983;178573982	chr2:179438711;179438710;179438709
Novex-2	15177	45754;45755;45756	chr2:178573984;178573983;178573982	chr2:179438711;179438710;179438709
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-131
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.3295
• 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
E/G	rs771209223	-1.032	0.896	D	0.61	0.604	0.686624564747	gnomAD-2.1.1	8.06E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.21199E-04	None	0	0	1.66279E-04
E/G	rs771209223	-1.032	0.896	D	0.61	0.604	0.686624564747	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	6.21633E-04	0
E/G	rs771209223	-1.032	0.896	D	0.61	0.604	0.686624564747	gnomAD-4.0.0	3.40915E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.60046E-04	6.40656E-05
E/K	None	None	0.026	N	0.411	0.288	0.406668915854	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-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
E/A	0.1443	likely_benign	0.1468	benign	-0.315	Destabilizing	0.896	D	0.514	neutral	D	0.523805343	None	None	N
E/C	0.8048	likely_pathogenic	0.7881	pathogenic	-0.181	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
E/D	0.1429	likely_benign	0.14	benign	-1.523	Destabilizing	0.011	N	0.253	neutral	N	0.46104473	None	None	N
E/F	0.6942	likely_pathogenic	0.6891	pathogenic	0.512	Stabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
E/G	0.2023	likely_benign	0.1843	benign	-0.791	Destabilizing	0.896	D	0.61	neutral	D	0.52891964	None	None	N
E/H	0.4537	ambiguous	0.4204	ambiguous	0.167	Stabilizing	0.999	D	0.581	neutral	None	None	None	None	N
E/I	0.3265	likely_benign	0.3382	benign	1.009	Stabilizing	0.988	D	0.72	prob.delet.	None	None	None	None	N
E/K	0.2238	likely_benign	0.2143	benign	-0.347	Destabilizing	0.026	N	0.411	neutral	N	0.500755125	None	None	N
E/L	0.3667	ambiguous	0.3846	ambiguous	1.009	Stabilizing	0.976	D	0.671	neutral	None	None	None	None	N
E/M	0.4224	ambiguous	0.4427	ambiguous	1.456	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
E/N	0.2776	likely_benign	0.2822	benign	-1.101	Destabilizing	0.851	D	0.527	neutral	None	None	None	None	N
E/P	0.7864	likely_pathogenic	0.7506	pathogenic	0.591	Stabilizing	0.988	D	0.665	neutral	None	None	None	None	N
E/Q	0.1515	likely_benign	0.1449	benign	-0.82	Destabilizing	0.896	D	0.537	neutral	N	0.486074858	None	None	N
E/R	0.3352	likely_benign	0.3014	benign	-0.149	Destabilizing	0.952	D	0.561	neutral	None	None	None	None	N
E/S	0.2068	likely_benign	0.206	benign	-1.47	Destabilizing	0.919	D	0.472	neutral	None	None	None	None	N
E/T	0.2057	likely_benign	0.208	benign	-1.043	Destabilizing	0.976	D	0.625	neutral	None	None	None	None	N
E/V	0.1823	likely_benign	0.1911	benign	0.591	Stabilizing	0.984	D	0.651	neutral	N	0.4890146	None	None	N
E/W	0.8649	likely_pathogenic	0.8469	pathogenic	0.689	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	N
E/Y	0.6144	likely_pathogenic	0.5983	pathogenic	0.802	Stabilizing	0.996	D	0.701	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.