TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30966	93121;93122;93123	chr2:178548730;178548729;178548728	chr2:179413457;179413456;179413455
N2AB	29325	88198;88199;88200	chr2:178548730;178548729;178548728	chr2:179413457;179413456;179413455
N2A	28398	85417;85418;85419	chr2:178548730;178548729;178548728	chr2:179413457;179413456;179413455
N2B	21901	65926;65927;65928	chr2:178548730;178548729;178548728	chr2:179413457;179413456;179413455
Novex-1	22026	66301;66302;66303	chr2:178548730;178548729;178548728	chr2:179413457;179413456;179413455
Novex-2	22093	66502;66503;66504	chr2:178548730;178548729;178548728	chr2:179413457;179413456;179413455
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-150
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.3706
• 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/I	None	None	0.999	N	0.503	0.355	0.655567208272	gnomAD-4.0.0	3.18272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71634E-06	0	0
L/P	None	None	1.0	D	0.831	0.805	0.865153388441	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88395E-05	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
L/A	0.7887	likely_pathogenic	0.7893	pathogenic	-1.987	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
L/C	0.879	likely_pathogenic	0.877	pathogenic	-1.578	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/D	0.9714	likely_pathogenic	0.972	pathogenic	-0.931	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/E	0.9243	likely_pathogenic	0.925	pathogenic	-0.804	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/F	0.3867	ambiguous	0.3904	ambiguous	-1.232	Destabilizing	1.0	D	0.724	prob.delet.	N	0.501441451	None	None	N
L/G	0.9384	likely_pathogenic	0.935	pathogenic	-2.437	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/H	0.8587	likely_pathogenic	0.8478	pathogenic	-1.672	Destabilizing	1.0	D	0.816	deleterious	D	0.537676415	None	None	N
L/I	0.1082	likely_benign	0.119	benign	-0.762	Destabilizing	0.999	D	0.503	neutral	N	0.516476726	None	None	N
L/K	0.9105	likely_pathogenic	0.9028	pathogenic	-1.308	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/M	0.252	likely_benign	0.2581	benign	-0.817	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/N	0.9086	likely_pathogenic	0.9083	pathogenic	-1.34	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/P	0.6454	likely_pathogenic	0.6622	pathogenic	-1.142	Destabilizing	1.0	D	0.831	deleterious	D	0.52606662	None	None	N
L/Q	0.8273	likely_pathogenic	0.8113	pathogenic	-1.291	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/R	0.8591	likely_pathogenic	0.8475	pathogenic	-0.999	Destabilizing	1.0	D	0.831	deleterious	D	0.54877923	None	None	N
L/S	0.9037	likely_pathogenic	0.8984	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/T	0.7244	likely_pathogenic	0.7249	pathogenic	-1.898	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/V	0.1539	likely_benign	0.1643	benign	-1.142	Destabilizing	0.999	D	0.513	neutral	D	0.525136281	None	None	N
L/W	0.7722	likely_pathogenic	0.7602	pathogenic	-1.341	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/Y	0.8167	likely_pathogenic	0.8074	pathogenic	-1.093	Destabilizing	1.0	D	0.816	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.