TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23278	70057;70058;70059	chr2:178576300;178576299;178576298	chr2:179441027;179441026;179441025
N2AB	21637	65134;65135;65136	chr2:178576300;178576299;178576298	chr2:179441027;179441026;179441025
N2A	20710	62353;62354;62355	chr2:178576300;178576299;178576298	chr2:179441027;179441026;179441025
N2B	14213	42862;42863;42864	chr2:178576300;178576299;178576298	chr2:179441027;179441026;179441025
Novex-1	14338	43237;43238;43239	chr2:178576300;178576299;178576298	chr2:179441027;179441026;179441025
Novex-2	14405	43438;43439;43440	chr2:178576300;178576299;178576298	chr2:179441027;179441026;179441025
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: Fn3-57
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1539
• 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/A	None	None	0.999	D	0.697	0.565	0.431602765429	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	None	None	0.999	N	0.684	0.327	0.341226946553	gnomAD-4.0.0	1.65683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94083E-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	0.6256	likely_pathogenic	0.6363	pathogenic	-2.262	Highly Destabilizing	0.999	D	0.697	prob.neutral	D	0.540787291	None	None	N
E/C	0.9422	likely_pathogenic	0.9464	pathogenic	-1.402	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/D	0.7001	likely_pathogenic	0.7384	pathogenic	-1.834	Destabilizing	0.999	D	0.645	neutral	N	0.491830124	None	None	N
E/F	0.9489	likely_pathogenic	0.9509	pathogenic	-1.908	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/G	0.739	likely_pathogenic	0.7536	pathogenic	-2.626	Highly Destabilizing	1.0	D	0.762	deleterious	D	0.524457463	None	None	N
E/H	0.8854	likely_pathogenic	0.8893	pathogenic	-1.8	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/I	0.9153	likely_pathogenic	0.9085	pathogenic	-1.196	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.7929	likely_pathogenic	0.7874	pathogenic	-2.319	Highly Destabilizing	0.999	D	0.684	prob.neutral	N	0.507590521	None	None	N
E/L	0.9	likely_pathogenic	0.8982	pathogenic	-1.196	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/M	0.8543	likely_pathogenic	0.8641	pathogenic	-0.366	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/N	0.9048	likely_pathogenic	0.9119	pathogenic	-2.387	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/P	0.9993	likely_pathogenic	0.9993	pathogenic	-1.541	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Q	0.3362	likely_benign	0.3381	benign	-2.108	Highly Destabilizing	1.0	D	0.747	deleterious	N	0.477129229	None	None	N
E/R	0.843	likely_pathogenic	0.8377	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/S	0.6674	likely_pathogenic	0.6807	pathogenic	-3.109	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/T	0.8353	likely_pathogenic	0.8427	pathogenic	-2.767	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/V	0.8083	likely_pathogenic	0.8075	pathogenic	-1.541	Destabilizing	1.0	D	0.766	deleterious	N	0.518835149	None	None	N
E/W	0.9729	likely_pathogenic	0.9742	pathogenic	-1.941	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.9218	likely_pathogenic	0.9241	pathogenic	-1.781	Destabilizing	1.0	D	0.788	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.