TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31430	94513;94514;94515	chr2:178547237;178547236;178547235	chr2:179411964;179411963;179411962
N2AB	29789	89590;89591;89592	chr2:178547237;178547236;178547235	chr2:179411964;179411963;179411962
N2A	28862	86809;86810;86811	chr2:178547237;178547236;178547235	chr2:179411964;179411963;179411962
N2B	22365	67318;67319;67320	chr2:178547237;178547236;178547235	chr2:179411964;179411963;179411962
Novex-1	22490	67693;67694;67695	chr2:178547237;178547236;178547235	chr2:179411964;179411963;179411962
Novex-2	22557	67894;67895;67896	chr2:178547237;178547236;178547235	chr2:179411964;179411963;179411962
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: Fn3-117
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.6166
• 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/G	rs1697596654	None	0.978	N	0.656	0.432	0.470566500458	gnomAD-4.0.0	1.5913E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8585E-06	0	0
E/K	rs868051341	None	0.978	N	0.554	0.403	0.303453137403	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs868051341	None	0.978	N	0.554	0.403	0.303453137403	gnomAD-4.0.0	3.04484E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.61477E-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
E/A	0.2921	likely_benign	0.3073	benign	-0.513	Destabilizing	0.989	D	0.654	neutral	N	0.474461453	None	None	I
E/C	0.9216	likely_pathogenic	0.9206	pathogenic	-0.203	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
E/D	0.1671	likely_benign	0.1719	benign	-0.469	Destabilizing	0.054	N	0.183	neutral	N	0.440194163	None	None	I
E/F	0.9175	likely_pathogenic	0.9173	pathogenic	-0.356	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
E/G	0.2864	likely_benign	0.3233	benign	-0.737	Destabilizing	0.978	D	0.656	neutral	N	0.473347475	None	None	I
E/H	0.7249	likely_pathogenic	0.7377	pathogenic	-0.223	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
E/I	0.6752	likely_pathogenic	0.694	pathogenic	0.056	Stabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
E/K	0.3673	ambiguous	0.444	ambiguous	-0.075	Destabilizing	0.978	D	0.554	neutral	N	0.46097208	None	None	I
E/L	0.6292	likely_pathogenic	0.6317	pathogenic	0.056	Stabilizing	0.998	D	0.751	deleterious	None	None	None	None	I
E/M	0.6509	likely_pathogenic	0.6685	pathogenic	0.173	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
E/N	0.3942	ambiguous	0.434	ambiguous	-0.279	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	I
E/P	0.8985	likely_pathogenic	0.9137	pathogenic	-0.113	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	I
E/Q	0.2342	likely_benign	0.2587	benign	-0.237	Destabilizing	0.997	D	0.629	neutral	N	0.504570929	None	None	I
E/R	0.5368	ambiguous	0.5889	pathogenic	0.201	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	I
E/S	0.3493	ambiguous	0.3789	ambiguous	-0.493	Destabilizing	0.983	D	0.569	neutral	None	None	None	None	I
E/T	0.406	ambiguous	0.4306	ambiguous	-0.321	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	I
E/V	0.4343	ambiguous	0.453	ambiguous	-0.113	Destabilizing	0.999	D	0.75	deleterious	N	0.515385355	None	None	I
E/W	0.9663	likely_pathogenic	0.9647	pathogenic	-0.206	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
E/Y	0.8529	likely_pathogenic	0.8561	pathogenic	-0.133	Destabilizing	1.0	D	0.75	deleterious	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.