TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18823	56692;56693;56694	chr2:178599326;178599325;178599324	chr2:179464053;179464052;179464051
N2AB	17182	51769;51770;51771	chr2:178599326;178599325;178599324	chr2:179464053;179464052;179464051
N2A	16255	48988;48989;48990	chr2:178599326;178599325;178599324	chr2:179464053;179464052;179464051
N2B	9758	29497;29498;29499	chr2:178599326;178599325;178599324	chr2:179464053;179464052;179464051
Novex-1	9883	29872;29873;29874	chr2:178599326;178599325;178599324	chr2:179464053;179464052;179464051
Novex-2	9950	30073;30074;30075	chr2:178599326;178599325;178599324	chr2:179464053;179464052;179464051
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-24
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.1106
• 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
E/K	rs745380159	-2.381	0.998	N	0.682	0.419	0.392702134506	gnomAD-2.1.1	7.22E-06	None	None	None	None	N	None	4.15E-05	0	None	0	0	None	3.32E-05	None	0	0	0
E/K	rs745380159	-2.381	0.998	N	0.682	0.419	0.392702134506	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs745380159	-2.381	0.998	N	0.682	0.419	0.392702134506	gnomAD-4.0.0	1.02963E-05	None	None	None	None	N	None	1.69693E-05	0	None	0	0	None	0	4.5045E-04	0	6.77287E-05	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	0.6638	likely_pathogenic	0.5537	ambiguous	-2.1	Highly Destabilizing	0.998	D	0.733	prob.delet.	D	0.523505957	None	None	N
E/C	0.9599	likely_pathogenic	0.9376	pathogenic	-1.318	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/D	0.7186	likely_pathogenic	0.6898	pathogenic	-2.013	Highly Destabilizing	0.434	N	0.367	neutral	N	0.476688383	None	None	N
E/F	0.9529	likely_pathogenic	0.9294	pathogenic	-1.739	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
E/G	0.8014	likely_pathogenic	0.7064	pathogenic	-2.455	Highly Destabilizing	0.999	D	0.763	deleterious	N	0.518697018	None	None	N
E/H	0.8735	likely_pathogenic	0.8293	pathogenic	-1.634	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/I	0.8825	likely_pathogenic	0.8156	pathogenic	-1.062	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/K	0.7323	likely_pathogenic	0.6257	pathogenic	-2.26	Highly Destabilizing	0.998	D	0.682	prob.neutral	N	0.497550889	None	None	N
E/L	0.8172	likely_pathogenic	0.7429	pathogenic	-1.062	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/M	0.7869	likely_pathogenic	0.7142	pathogenic	-0.291	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/N	0.8901	likely_pathogenic	0.8535	pathogenic	-2.38	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9992	pathogenic	-1.398	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Q	0.2504	likely_benign	0.1975	benign	-2.084	Highly Destabilizing	0.999	D	0.775	deleterious	N	0.51465185	None	None	N
E/R	0.8104	likely_pathogenic	0.7221	pathogenic	-1.976	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/S	0.6775	likely_pathogenic	0.5805	pathogenic	-3.024	Highly Destabilizing	0.997	D	0.697	prob.neutral	None	None	None	None	N
E/T	0.8111	likely_pathogenic	0.7201	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/V	0.7441	likely_pathogenic	0.6325	pathogenic	-1.398	Destabilizing	1.0	D	0.799	deleterious	N	0.509289269	None	None	N
E/W	0.9733	likely_pathogenic	0.9639	pathogenic	-1.83	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/Y	0.9301	likely_pathogenic	0.897	pathogenic	-1.635	Destabilizing	1.0	D	0.832	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.