TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31784	95575;95576;95577	chr2:178545886;178545885;178545884	chr2:179410613;179410612;179410611
N2AB	30143	90652;90653;90654	chr2:178545886;178545885;178545884	chr2:179410613;179410612;179410611
N2A	29216	87871;87872;87873	chr2:178545886;178545885;178545884	chr2:179410613;179410612;179410611
N2B	22719	68380;68381;68382	chr2:178545886;178545885;178545884	chr2:179410613;179410612;179410611
Novex-1	22844	68755;68756;68757	chr2:178545886;178545885;178545884	chr2:179410613;179410612;179410611
Novex-2	22911	68956;68957;68958	chr2:178545886;178545885;178545884	chr2:179410613;179410612;179410611
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-119
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.0926
• 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
A/T	None	None	0.946	D	0.702	0.789	0.676012115908	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
A/V	rs1553520967	None	0.946	D	0.68	0.69	0.663723012633	Palmio (2019)	None	HMERF	het	None	None	N	Genetic analysis of genes in 12 HMERF families; co-segregates with condition (n = 6, 6 affected (8 total))	None	None	None	None	None	None	None	None	None	None	None

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
A/C	0.8605	likely_pathogenic	0.84	pathogenic	-1.76	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
A/D	0.9933	likely_pathogenic	0.9942	pathogenic	-2.819	Highly Destabilizing	0.988	D	0.838	deleterious	None	None	None	None	N
A/E	0.9925	likely_pathogenic	0.9929	pathogenic	-2.604	Highly Destabilizing	0.984	D	0.807	deleterious	D	0.662217087	None	None	N
A/F	0.9876	likely_pathogenic	0.9859	pathogenic	-0.587	Destabilizing	0.996	D	0.877	deleterious	None	None	None	None	N
A/G	0.1238	likely_benign	0.125	benign	-2.069	Highly Destabilizing	0.004	N	0.379	neutral	D	0.544722131	None	None	N
A/H	0.9962	likely_pathogenic	0.9963	pathogenic	-2.052	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
A/I	0.9751	likely_pathogenic	0.9708	pathogenic	-0.498	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
A/K	0.9983	likely_pathogenic	0.9984	pathogenic	-1.453	Destabilizing	0.988	D	0.802	deleterious	None	None	None	None	N
A/L	0.9209	likely_pathogenic	0.9194	pathogenic	-0.498	Destabilizing	0.959	D	0.811	deleterious	None	None	None	None	N
A/M	0.9552	likely_pathogenic	0.9503	pathogenic	-1.013	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
A/N	0.9847	likely_pathogenic	0.9854	pathogenic	-1.893	Destabilizing	0.976	D	0.845	deleterious	None	None	None	None	N
A/P	0.6176	likely_pathogenic	0.6679	pathogenic	-0.853	Destabilizing	0.995	D	0.819	deleterious	D	0.613291066	None	None	N
A/Q	0.9887	likely_pathogenic	0.9892	pathogenic	-1.61	Destabilizing	0.996	D	0.804	deleterious	None	None	None	None	N
A/R	0.9943	likely_pathogenic	0.9948	pathogenic	-1.533	Destabilizing	0.988	D	0.818	deleterious	None	None	None	None	N
A/S	0.3771	ambiguous	0.3577	ambiguous	-2.227	Highly Destabilizing	0.896	D	0.619	neutral	D	0.585442026	None	None	N
A/T	0.8176	likely_pathogenic	0.8058	pathogenic	-1.913	Destabilizing	0.946	D	0.702	prob.neutral	D	0.629138983	None	None	N
A/V	0.874	likely_pathogenic	0.8651	pathogenic	-0.853	Destabilizing	0.946	D	0.68	prob.neutral	D	0.635266345	None	None	N
A/W	0.9982	likely_pathogenic	0.9982	pathogenic	-1.278	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
A/Y	0.9939	likely_pathogenic	0.9933	pathogenic	-0.992	Destabilizing	0.996	D	0.885	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.