TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16225	48898;48899;48900	chr2:178614934;178614933;178614932	chr2:179479661;179479660;179479659
N2AB	14584	43975;43976;43977	chr2:178614934;178614933;178614932	chr2:179479661;179479660;179479659
N2A	13657	41194;41195;41196	chr2:178614934;178614933;178614932	chr2:179479661;179479660;179479659
N2B	7160	21703;21704;21705	chr2:178614934;178614933;178614932	chr2:179479661;179479660;179479659
Novex-1	7285	22078;22079;22080	chr2:178614934;178614933;178614932	chr2:179479661;179479660;179479659
Novex-2	7352	22279;22280;22281	chr2:178614934;178614933;178614932	chr2:179479661;179479660;179479659
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: Fn3-5
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0975
• 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	rs781080078	-2.483	1.0	D	0.851	0.858	0.804125093776	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.03E-05	0
Y/H	rs781080078	-2.483	1.0	D	0.851	0.858	0.804125093776	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs781080078	-2.483	1.0	D	0.851	0.858	0.804125093776	gnomAD-4.0.0	3.93481E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.34804E-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	0.9853	likely_pathogenic	0.9863	pathogenic	-3.305	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/C	0.8465	likely_pathogenic	0.8742	pathogenic	-1.766	Destabilizing	1.0	D	0.876	deleterious	D	0.791806324	None	None	N
Y/D	0.9715	likely_pathogenic	0.9724	pathogenic	-3.874	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.821204068	None	None	N
Y/E	0.9914	likely_pathogenic	0.9913	pathogenic	-3.661	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/F	0.1463	likely_benign	0.1592	benign	-1.423	Destabilizing	0.999	D	0.746	deleterious	D	0.697952648	None	None	N
Y/G	0.9691	likely_pathogenic	0.9673	pathogenic	-3.701	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/H	0.8077	likely_pathogenic	0.8231	pathogenic	-2.474	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.749644681	None	None	N
Y/I	0.9407	likely_pathogenic	0.9486	pathogenic	-1.961	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9954	likely_pathogenic	0.9951	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/L	0.8853	likely_pathogenic	0.8899	pathogenic	-1.961	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
Y/M	0.9507	likely_pathogenic	0.9545	pathogenic	-1.59	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/N	0.865	likely_pathogenic	0.8667	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.821532956	None	None	N
Y/P	0.9991	likely_pathogenic	0.9989	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.988	likely_pathogenic	0.9882	pathogenic	-3.148	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/R	0.9877	likely_pathogenic	0.9874	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/S	0.9503	likely_pathogenic	0.9547	pathogenic	-3.666	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.821204068	None	None	N
Y/T	0.9832	likely_pathogenic	0.9847	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/V	0.9039	likely_pathogenic	0.9165	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/W	0.6347	likely_pathogenic	0.6497	pathogenic	-0.733	Destabilizing	1.0	D	0.828	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.