TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7611	23056;23057;23058	chr2:178721188;178721187;178721186	chr2:179585915;179585914;179585913
N2AB	7294	22105;22106;22107	chr2:178721188;178721187;178721186	chr2:179585915;179585914;179585913
N2A	6367	19324;19325;19326	chr2:178721188;178721187;178721186	chr2:179585915;179585914;179585913
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-61
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4358
• 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
V/I	rs2078303189	None	None	N	0.113	0.119	0.204665344411	gnomAD-4.0.0	1.63227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94507E-06	0	0
V/L	None	None	0.02	N	0.345	0.108	0.283371740733	gnomAD-4.0.0	1.63227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94507E-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
V/A	0.4336	ambiguous	0.2909	benign	-0.908	Destabilizing	0.055	N	0.411	neutral	N	0.46679493	None	None	N
V/C	0.8774	likely_pathogenic	0.819	pathogenic	-0.726	Destabilizing	0.909	D	0.517	neutral	None	None	None	None	N
V/D	0.7694	likely_pathogenic	0.6321	pathogenic	-0.66	Destabilizing	0.497	N	0.623	neutral	N	0.454984552	None	None	N
V/E	0.6324	likely_pathogenic	0.5035	ambiguous	-0.71	Destabilizing	0.567	D	0.547	neutral	None	None	None	None	N
V/F	0.2491	likely_benign	0.2101	benign	-0.745	Destabilizing	0.497	N	0.51	neutral	N	0.482924175	None	None	N
V/G	0.4595	ambiguous	0.3345	benign	-1.139	Destabilizing	0.497	N	0.549	neutral	N	0.502131294	None	None	N
V/H	0.7487	likely_pathogenic	0.662	pathogenic	-0.539	Destabilizing	0.968	D	0.643	neutral	None	None	None	None	N
V/I	0.0707	likely_benign	0.0648	benign	-0.411	Destabilizing	None	N	0.113	neutral	N	0.449223786	None	None	N
V/K	0.6876	likely_pathogenic	0.5653	pathogenic	-0.862	Destabilizing	0.567	D	0.556	neutral	None	None	None	None	N
V/L	0.2107	likely_benign	0.1498	benign	-0.411	Destabilizing	0.02	N	0.345	neutral	N	0.489896973	None	None	N
V/M	0.2124	likely_benign	0.1603	benign	-0.43	Destabilizing	0.567	D	0.481	neutral	None	None	None	None	N
V/N	0.5211	ambiguous	0.3736	ambiguous	-0.634	Destabilizing	0.567	D	0.63	neutral	None	None	None	None	N
V/P	0.8976	likely_pathogenic	0.7914	pathogenic	-0.541	Destabilizing	0.726	D	0.607	neutral	None	None	None	None	N
V/Q	0.5307	ambiguous	0.4146	ambiguous	-0.83	Destabilizing	0.726	D	0.597	neutral	None	None	None	None	N
V/R	0.6068	likely_pathogenic	0.4842	ambiguous	-0.29	Destabilizing	0.567	D	0.62	neutral	None	None	None	None	N
V/S	0.3928	ambiguous	0.2869	benign	-1.072	Destabilizing	0.157	N	0.491	neutral	None	None	None	None	N
V/T	0.2955	likely_benign	0.2172	benign	-1.018	Destabilizing	0.001	N	0.175	neutral	None	None	None	None	N
V/W	0.8695	likely_pathogenic	0.826	pathogenic	-0.865	Destabilizing	0.968	D	0.694	prob.neutral	None	None	None	None	N
V/Y	0.686	likely_pathogenic	0.6099	pathogenic	-0.59	Destabilizing	0.726	D	0.503	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.