TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16721	50386;50387;50388	chr2:178612364;178612363;178612362	chr2:179477091;179477090;179477089
N2AB	15080	45463;45464;45465	chr2:178612364;178612363;178612362	chr2:179477091;179477090;179477089
N2A	14153	42682;42683;42684	chr2:178612364;178612363;178612362	chr2:179477091;179477090;179477089
N2B	7656	23191;23192;23193	chr2:178612364;178612363;178612362	chr2:179477091;179477090;179477089
Novex-1	7781	23566;23567;23568	chr2:178612364;178612363;178612362	chr2:179477091;179477090;179477089
Novex-2	7848	23767;23768;23769	chr2:178612364;178612363;178612362	chr2:179477091;179477090;179477089
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: Fn3-9
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0841
• 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/C	None	None	1.0	D	0.863	0.884	0.926672064637	gnomAD-4.0.0	1.36945E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79979E-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	0.9937	likely_pathogenic	0.9945	pathogenic	-3.033	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/C	0.9294	likely_pathogenic	0.9482	pathogenic	-1.803	Destabilizing	1.0	D	0.863	deleterious	D	0.774651026	None	None	N
Y/D	0.9978	likely_pathogenic	0.9983	pathogenic	-2.942	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.805686645	None	None	N
Y/E	0.9992	likely_pathogenic	0.9993	pathogenic	-2.738	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/F	0.2621	likely_benign	0.2896	benign	-1.061	Destabilizing	0.999	D	0.757	deleterious	D	0.645266637	None	None	N
Y/G	0.9902	likely_pathogenic	0.9902	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/H	0.9736	likely_pathogenic	0.9815	pathogenic	-1.966	Destabilizing	1.0	D	0.824	deleterious	D	0.774651026	None	None	N
Y/I	0.969	likely_pathogenic	0.9705	pathogenic	-1.656	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/K	0.9991	likely_pathogenic	0.9994	pathogenic	-1.933	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/L	0.9278	likely_pathogenic	0.928	pathogenic	-1.656	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
Y/M	0.9796	likely_pathogenic	0.9843	pathogenic	-1.508	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9813	likely_pathogenic	0.9847	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.806001082	None	None	N
Y/P	0.9987	likely_pathogenic	0.9983	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/Q	0.9982	likely_pathogenic	0.9987	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/R	0.9968	likely_pathogenic	0.9973	pathogenic	-1.672	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/S	0.983	likely_pathogenic	0.9844	pathogenic	-3.089	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.805686645	None	None	N
Y/T	0.9936	likely_pathogenic	0.994	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/V	0.9393	likely_pathogenic	0.9379	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/W	0.8485	likely_pathogenic	0.8859	pathogenic	-0.303	Destabilizing	1.0	D	0.807	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.