TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19879	59860;59861;59862	chr2:178592269;178592268;178592267	chr2:179456996;179456995;179456994
N2AB	18238	54937;54938;54939	chr2:178592269;178592268;178592267	chr2:179456996;179456995;179456994
N2A	17311	52156;52157;52158	chr2:178592269;178592268;178592267	chr2:179456996;179456995;179456994
N2B	10814	32665;32666;32667	chr2:178592269;178592268;178592267	chr2:179456996;179456995;179456994
Novex-1	10939	33040;33041;33042	chr2:178592269;178592268;178592267	chr2:179456996;179456995;179456994
Novex-2	11006	33241;33242;33243	chr2:178592269;178592268;178592267	chr2:179456996;179456995;179456994
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-32
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.197
• 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
G/E	rs745418262	-2.125	1.0	N	0.866	0.362	0.43656330218	gnomAD-2.1.1	1.24E-05	None	None	None	None	N	None	0	8.95E-05	None	0	0	None	0	None	0	0	0
G/E	rs745418262	-2.125	1.0	N	0.866	0.362	0.43656330218	gnomAD-4.0.0	4.80383E-06	None	None	None	None	N	None	0	6.97869E-05	None	0	0	None	0	0	0	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
G/A	0.2668	likely_benign	0.2879	benign	-0.898	Destabilizing	1.0	D	0.719	prob.delet.	N	0.493396606	None	None	N
G/C	0.508	ambiguous	0.5804	pathogenic	-1.13	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
G/D	0.6969	likely_pathogenic	0.7473	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/E	0.7176	likely_pathogenic	0.7693	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.866	deleterious	N	0.492382648	None	None	N
G/F	0.8549	likely_pathogenic	0.8968	pathogenic	-1.216	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/H	0.8256	likely_pathogenic	0.8789	pathogenic	-1.569	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/I	0.8024	likely_pathogenic	0.8625	pathogenic	-0.479	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/K	0.8619	likely_pathogenic	0.8992	pathogenic	-1.501	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/L	0.6852	likely_pathogenic	0.734	pathogenic	-0.479	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
G/M	0.7908	likely_pathogenic	0.8381	pathogenic	-0.384	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/N	0.6489	likely_pathogenic	0.7088	pathogenic	-1.28	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/P	0.9854	likely_pathogenic	0.9901	pathogenic	-0.58	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/Q	0.7434	likely_pathogenic	0.8003	pathogenic	-1.493	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/R	0.7796	likely_pathogenic	0.8411	pathogenic	-1.151	Destabilizing	1.0	D	0.863	deleterious	N	0.50525989	None	None	N
G/S	0.1764	likely_benign	0.2016	benign	-1.419	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/T	0.4751	ambiguous	0.5719	pathogenic	-1.405	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/V	0.7022	likely_pathogenic	0.7833	pathogenic	-0.58	Destabilizing	1.0	D	0.873	deleterious	N	0.494917543	None	None	N
G/W	0.8356	likely_pathogenic	0.8843	pathogenic	-1.629	Destabilizing	1.0	D	0.781	deleterious	N	0.518048227	None	None	N
G/Y	0.8004	likely_pathogenic	0.8568	pathogenic	-1.232	Destabilizing	1.0	D	0.857	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.