TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17400	52423;52424;52425	chr2:178608813;178608812;178608811	chr2:179473540;179473539;179473538
N2AB	15759	47500;47501;47502	chr2:178608813;178608812;178608811	chr2:179473540;179473539;179473538
N2A	14832	44719;44720;44721	chr2:178608813;178608812;178608811	chr2:179473540;179473539;179473538
N2B	8335	25228;25229;25230	chr2:178608813;178608812;178608811	chr2:179473540;179473539;179473538
Novex-1	8460	25603;25604;25605	chr2:178608813;178608812;178608811	chr2:179473540;179473539;179473538
Novex-2	8527	25804;25805;25806	chr2:178608813;178608812;178608811	chr2:179473540;179473539;179473538
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: Fn3-14
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.9052
• Predicted PPI site: I

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/A	rs773027240	-0.141	0.999	N	0.613	0.54	0.414539908741	gnomAD-2.1.1	2.86E-05	None	None	None	None	I	None	4.14E-05	0	None	0	0	None	0	None	0	5.47E-05	0
E/A	rs773027240	-0.141	0.999	N	0.613	0.54	0.414539908741	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	8.83E-05	0	0
E/A	rs773027240	-0.141	0.999	N	0.613	0.54	0.414539908741	gnomAD-4.0.0	1.2217E-04	None	None	None	None	I	None	6.68074E-05	0	None	0	0	None	0	0	1.61116E-04	0	3.20513E-05

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	0.2853	likely_benign	0.2832	benign	-0.461	Destabilizing	0.999	D	0.613	neutral	N	0.481291425	None	None	I
E/C	0.9219	likely_pathogenic	0.9175	pathogenic	-0.142	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
E/D	0.1392	likely_benign	0.1527	benign	-0.408	Destabilizing	0.999	D	0.45	neutral	N	0.469727637	None	None	I
E/F	0.9289	likely_pathogenic	0.9209	pathogenic	-0.206	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	I
E/G	0.3859	ambiguous	0.3733	ambiguous	-0.686	Destabilizing	1.0	D	0.603	neutral	N	0.504515001	None	None	I
E/H	0.7117	likely_pathogenic	0.6944	pathogenic	-0.019	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
E/I	0.6513	likely_pathogenic	0.6508	pathogenic	0.107	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	I
E/K	0.3603	ambiguous	0.3491	ambiguous	0.232	Stabilizing	0.999	D	0.601	neutral	N	0.430939962	None	None	I
E/L	0.6908	likely_pathogenic	0.6746	pathogenic	0.107	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	I
E/M	0.7222	likely_pathogenic	0.7037	pathogenic	0.206	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	I
E/N	0.3996	ambiguous	0.407	ambiguous	-0.187	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
E/P	0.4962	ambiguous	0.4943	ambiguous	-0.062	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	I
E/Q	0.2654	likely_benign	0.2559	benign	-0.126	Destabilizing	1.0	D	0.602	neutral	N	0.50085862	None	None	I
E/R	0.5295	ambiguous	0.4995	ambiguous	0.47	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
E/S	0.3485	ambiguous	0.3458	ambiguous	-0.346	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	I
E/T	0.4272	ambiguous	0.4416	ambiguous	-0.157	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
E/V	0.4368	ambiguous	0.4339	ambiguous	-0.062	Destabilizing	1.0	D	0.653	neutral	N	0.474562016	None	None	I
E/W	0.9762	likely_pathogenic	0.9724	pathogenic	-0.008	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
E/Y	0.8541	likely_pathogenic	0.8443	pathogenic	0.045	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	I

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.