TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20655	62188;62189;62190	chr2:178589762;178589761;178589760	chr2:179454489;179454488;179454487
N2AB	19014	57265;57266;57267	chr2:178589762;178589761;178589760	chr2:179454489;179454488;179454487
N2A	18087	54484;54485;54486	chr2:178589762;178589761;178589760	chr2:179454489;179454488;179454487
N2B	11590	34993;34994;34995	chr2:178589762;178589761;178589760	chr2:179454489;179454488;179454487
Novex-1	11715	35368;35369;35370	chr2:178589762;178589761;178589760	chr2:179454489;179454488;179454487
Novex-2	11782	35569;35570;35571	chr2:178589762;178589761;178589760	chr2:179454489;179454488;179454487
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: Fn3-37
• Domain position: 87
• Structural Position: 122
• Q(SASA): 0.3216
• 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	rs776314797	-0.221	1.0	N	0.781	0.391	0.360565625551	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	3.27E-05	None	0	2.67E-05	0
E/K	rs776314797	-0.221	1.0	N	0.781	0.391	0.360565625551	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
E/K	rs776314797	-0.221	1.0	N	0.781	0.391	0.360565625551	gnomAD-4.0.0	4.46266E-05	None	None	None	None	N	None	5.34102E-05	1.66761E-05	None	0	0	None	0	0	5.25607E-05	4.39223E-05	1.60149E-05

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	0.695	likely_pathogenic	0.7218	pathogenic	-0.39	Destabilizing	0.997	D	0.785	deleterious	N	0.514475704	None	None	N
E/C	0.9838	likely_pathogenic	0.9843	pathogenic	-0.152	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/D	0.6319	likely_pathogenic	0.7045	pathogenic	-0.924	Destabilizing	0.997	D	0.729	deleterious	N	0.466997011	None	None	N
E/F	0.9833	likely_pathogenic	0.988	pathogenic	0.521	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/G	0.8675	likely_pathogenic	0.8879	pathogenic	-0.823	Destabilizing	0.999	D	0.739	deleterious	N	0.478570807	None	None	N
E/H	0.9577	likely_pathogenic	0.9645	pathogenic	0.37	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/I	0.8704	likely_pathogenic	0.8876	pathogenic	0.809	Stabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
E/K	0.8286	likely_pathogenic	0.7924	pathogenic	-0.253	Destabilizing	1.0	D	0.781	deleterious	N	0.476075591	None	None	N
E/L	0.9314	likely_pathogenic	0.9459	pathogenic	0.809	Stabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
E/M	0.9146	likely_pathogenic	0.9233	pathogenic	1.172	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/N	0.9154	likely_pathogenic	0.9327	pathogenic	-0.957	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/P	0.9774	likely_pathogenic	0.985	pathogenic	0.432	Stabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
E/Q	0.5644	likely_pathogenic	0.5797	pathogenic	-0.731	Destabilizing	1.0	D	0.752	deleterious	N	0.471480462	None	None	N
E/R	0.9053	likely_pathogenic	0.9183	pathogenic	0.057	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/S	0.8094	likely_pathogenic	0.8251	pathogenic	-1.32	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
E/T	0.8038	likely_pathogenic	0.8336	pathogenic	-0.938	Destabilizing	0.999	D	0.729	deleterious	None	None	None	None	N
E/V	0.7437	likely_pathogenic	0.7781	pathogenic	0.432	Stabilizing	0.999	D	0.777	deleterious	N	0.470328373	None	None	N
E/W	0.9963	likely_pathogenic	0.9971	pathogenic	0.784	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.9783	likely_pathogenic	0.9829	pathogenic	0.823	Stabilizing	1.0	D	0.867	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.