TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16035	48328;48329;48330	chr2:178616786;178616785;178616784	chr2:179481513;179481512;179481511
N2AB	14394	43405;43406;43407	chr2:178616786;178616785;178616784	chr2:179481513;179481512;179481511
N2A	13467	40624;40625;40626	chr2:178616786;178616785;178616784	chr2:179481513;179481512;179481511
N2B	6970	21133;21134;21135	chr2:178616786;178616785;178616784	chr2:179481513;179481512;179481511
Novex-1	7095	21508;21509;21510	chr2:178616786;178616785;178616784	chr2:179481513;179481512;179481511
Novex-2	7162	21709;21710;21711	chr2:178616786;178616785;178616784	chr2:179481513;179481512;179481511
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-109
• Domain position: 68
• Structural Position: 156
• Q(SASA): 0.0602
• 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
L/V	rs371209083	-0.804	0.898	N	0.705	0.148	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
L/V	rs371209083	-0.804	0.898	N	0.705	0.148	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
L/V	rs371209083	-0.804	0.898	N	0.705	0.148	None	gnomAD-4.0.0	5.13148E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.58589E-06	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
L/A	0.9184	likely_pathogenic	0.938	pathogenic	-2.373	Highly Destabilizing	0.983	D	0.763	deleterious	None	None	None	None	N
L/C	0.8681	likely_pathogenic	0.8867	pathogenic	-1.835	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9996	pathogenic	-2.038	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
L/E	0.9936	likely_pathogenic	0.9958	pathogenic	-1.848	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
L/F	0.6698	likely_pathogenic	0.7368	pathogenic	-1.475	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
L/G	0.9869	likely_pathogenic	0.9907	pathogenic	-2.904	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
L/H	0.9886	likely_pathogenic	0.9929	pathogenic	-2.252	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/I	0.1293	likely_benign	0.1511	benign	-0.866	Destabilizing	0.289	N	0.375	neutral	None	None	None	None	N
L/K	0.9874	likely_pathogenic	0.9914	pathogenic	-1.635	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
L/M	0.3057	likely_benign	0.356	ambiguous	-0.866	Destabilizing	0.993	D	0.765	deleterious	D	0.546260396	None	None	N
L/N	0.9944	likely_pathogenic	0.9959	pathogenic	-1.83	Destabilizing	0.999	D	0.896	deleterious	None	None	None	None	N
L/P	0.9923	likely_pathogenic	0.9951	pathogenic	-1.345	Destabilizing	0.999	D	0.896	deleterious	D	0.58705554	None	None	N
L/Q	0.9735	likely_pathogenic	0.9822	pathogenic	-1.735	Destabilizing	1.0	D	0.895	deleterious	D	0.58705554	None	None	N
L/R	0.9754	likely_pathogenic	0.9832	pathogenic	-1.36	Destabilizing	0.999	D	0.891	deleterious	D	0.58705554	None	None	N
L/S	0.9894	likely_pathogenic	0.9929	pathogenic	-2.651	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
L/T	0.9558	likely_pathogenic	0.9696	pathogenic	-2.302	Highly Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
L/V	0.1512	likely_benign	0.1859	benign	-1.345	Destabilizing	0.898	D	0.705	prob.neutral	N	0.444991435	None	None	N
L/W	0.9542	likely_pathogenic	0.9728	pathogenic	-1.726	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/Y	0.9622	likely_pathogenic	0.9757	pathogenic	-1.455	Destabilizing	0.999	D	0.834	deleterious	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.