TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23959	72100;72101;72102	chr2:178574257;178574256;178574255	chr2:179438984;179438983;179438982
N2AB	22318	67177;67178;67179	chr2:178574257;178574256;178574255	chr2:179438984;179438983;179438982
N2A	21391	64396;64397;64398	chr2:178574257;178574256;178574255	chr2:179438984;179438983;179438982
N2B	14894	44905;44906;44907	chr2:178574257;178574256;178574255	chr2:179438984;179438983;179438982
Novex-1	15019	45280;45281;45282	chr2:178574257;178574256;178574255	chr2:179438984;179438983;179438982
Novex-2	15086	45481;45482;45483	chr2:178574257;178574256;178574255	chr2:179438984;179438983;179438982
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-62
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.155
• 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
Y/H	None	None	1.0	D	0.815	0.77	0.643667808983	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
Y/A	0.99	likely_pathogenic	0.9903	pathogenic	-3.741	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
Y/C	0.8077	likely_pathogenic	0.8128	pathogenic	-1.946	Destabilizing	1.0	D	0.859	deleterious	D	0.661108061	None	None	N
Y/D	0.9944	likely_pathogenic	0.9937	pathogenic	-3.921	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.661309865	None	None	N
Y/E	0.9984	likely_pathogenic	0.9982	pathogenic	-3.706	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/F	0.2425	likely_benign	0.2422	benign	-1.656	Destabilizing	0.999	D	0.664	neutral	D	0.524585362	None	None	N
Y/G	0.9811	likely_pathogenic	0.9803	pathogenic	-4.132	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
Y/H	0.9525	likely_pathogenic	0.9457	pathogenic	-2.845	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.635368145	None	None	N
Y/I	0.9572	likely_pathogenic	0.957	pathogenic	-2.397	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.9974	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.9014	likely_pathogenic	0.902	pathogenic	-2.397	Highly Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
Y/M	0.9686	likely_pathogenic	0.9689	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/N	0.9577	likely_pathogenic	0.9527	pathogenic	-3.399	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.661309865	None	None	N
Y/P	0.9985	likely_pathogenic	0.9984	pathogenic	-2.867	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
Y/Q	0.996	likely_pathogenic	0.9958	pathogenic	-3.137	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/R	0.9899	likely_pathogenic	0.989	pathogenic	-2.38	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/S	0.9629	likely_pathogenic	0.9622	pathogenic	-3.687	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.661309865	None	None	N
Y/T	0.9882	likely_pathogenic	0.9877	pathogenic	-3.358	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9165	likely_pathogenic	0.9152	pathogenic	-2.867	Highly Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
Y/W	0.7852	likely_pathogenic	0.7972	pathogenic	-0.859	Destabilizing	1.0	D	0.794	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.