TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6670	20233;20234;20235	chr2:178727357;178727356;178727355	chr2:179592084;179592083;179592082
N2AB	6353	19282;19283;19284	chr2:178727357;178727356;178727355	chr2:179592084;179592083;179592082
N2A	5426	16501;16502;16503	chr2:178727357;178727356;178727355	chr2:179592084;179592083;179592082
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-51
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4789
• 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/A	None	None	0.003	N	0.101	0.144	0.300449992093	gnomAD-4.0.0	2.07413E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05413E-07	2.3955E-05	0
V/I	rs749601124	-0.185	0.008	N	0.169	0.052	0.24896430686	gnomAD-2.1.1	4.26E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.31E-06	0
V/I	rs749601124	-0.185	0.008	N	0.169	0.052	0.24896430686	gnomAD-4.0.0	1.38357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81148E-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	0.2155	likely_benign	0.2782	benign	-1.044	Destabilizing	0.003	N	0.101	neutral	N	0.456096961	None	None	N
V/C	0.7686	likely_pathogenic	0.8347	pathogenic	-0.708	Destabilizing	0.989	D	0.441	neutral	None	None	None	None	N
V/D	0.4189	ambiguous	0.6142	pathogenic	-0.825	Destabilizing	0.858	D	0.434	neutral	None	None	None	None	N
V/E	0.3005	likely_benign	0.4269	ambiguous	-0.855	Destabilizing	0.075	N	0.247	neutral	N	0.453236579	None	None	N
V/F	0.2037	likely_benign	0.2465	benign	-0.809	Destabilizing	0.923	D	0.426	neutral	None	None	None	None	N
V/G	0.2485	likely_benign	0.3186	benign	-1.301	Destabilizing	0.565	D	0.419	neutral	N	0.480241604	None	None	N
V/H	0.5647	likely_pathogenic	0.6668	pathogenic	-0.698	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	N
V/I	0.0766	likely_benign	0.0757	benign	-0.461	Destabilizing	0.008	N	0.169	neutral	N	0.429021873	None	None	N
V/K	0.4043	ambiguous	0.5574	ambiguous	-0.959	Destabilizing	0.923	D	0.423	neutral	None	None	None	None	N
V/L	0.1628	likely_benign	0.1902	benign	-0.461	Destabilizing	0.349	N	0.401	neutral	N	0.492321203	None	None	N
V/M	0.1711	likely_benign	0.1936	benign	-0.432	Destabilizing	0.923	D	0.41	neutral	None	None	None	None	N
V/N	0.3215	likely_benign	0.4266	ambiguous	-0.737	Destabilizing	0.961	D	0.517	neutral	None	None	None	None	N
V/P	0.7437	likely_pathogenic	0.7998	pathogenic	-0.62	Destabilizing	0.961	D	0.496	neutral	None	None	None	None	N
V/Q	0.2951	likely_benign	0.3727	ambiguous	-0.917	Destabilizing	0.923	D	0.5	neutral	None	None	None	None	N
V/R	0.3293	likely_benign	0.4869	ambiguous	-0.391	Destabilizing	0.923	D	0.519	neutral	None	None	None	None	N
V/S	0.2221	likely_benign	0.2892	benign	-1.187	Destabilizing	0.633	D	0.419	neutral	None	None	None	None	N
V/T	0.189	likely_benign	0.2495	benign	-1.111	Destabilizing	0.775	D	0.307	neutral	None	None	None	None	N
V/W	0.7923	likely_pathogenic	0.8529	pathogenic	-0.959	Destabilizing	0.996	D	0.656	neutral	None	None	None	None	N
V/Y	0.5656	likely_pathogenic	0.6583	pathogenic	-0.677	Destabilizing	0.987	D	0.412	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.