TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6912	20959;20960;20961	chr2:178725470;178725469;178725468	chr2:179590197;179590196;179590195
N2AB	6595	20008;20009;20010	chr2:178725470;178725469;178725468	chr2:179590197;179590196;179590195
N2A	5668	17227;17228;17229	chr2:178725470;178725469;178725468	chr2:179590197;179590196;179590195
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-53
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0493
• 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
L/I	rs879042542	-0.505	0.994	D	0.614	0.508	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
L/I	rs879042542	-0.505	0.994	D	0.614	0.508	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs780735199	-1.539	0.998	D	0.888	0.865	0.832001373036	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
L/P	rs780735199	-1.539	0.998	D	0.888	0.865	0.832001373036	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
L/P	rs780735199	-1.539	0.998	D	0.888	0.865	0.832001373036	gnomAD-4.0.0	2.56391E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.56966E-05	0	0	0	2.84706E-05

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
L/A	0.9144	likely_pathogenic	0.9291	pathogenic	-2.269	Highly Destabilizing	0.611	D	0.604	neutral	None	None	None	None	N
L/C	0.9	likely_pathogenic	0.9149	pathogenic	-1.614	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.161	Highly Destabilizing	0.46	N	0.744	deleterious	None	None	None	None	N
L/E	0.9969	likely_pathogenic	0.9979	pathogenic	-2.849	Highly Destabilizing	0.995	D	0.857	deleterious	None	None	None	None	N
L/F	0.5924	likely_pathogenic	0.6265	pathogenic	-1.455	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
L/G	0.9877	likely_pathogenic	0.9908	pathogenic	-2.831	Highly Destabilizing	0.992	D	0.851	deleterious	None	None	None	None	N
L/H	0.9897	likely_pathogenic	0.9928	pathogenic	-2.806	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/I	0.2314	likely_benign	0.2497	benign	-0.57	Destabilizing	0.994	D	0.614	neutral	D	0.535497141	None	None	N
L/K	0.9929	likely_pathogenic	0.9957	pathogenic	-1.815	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
L/M	0.3119	likely_benign	0.3547	ambiguous	-0.877	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
L/N	0.9973	likely_pathogenic	0.9982	pathogenic	-2.59	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
L/P	0.9973	likely_pathogenic	0.9983	pathogenic	-1.13	Destabilizing	0.998	D	0.888	deleterious	D	0.56141621	None	None	N
L/Q	0.9799	likely_pathogenic	0.9866	pathogenic	-2.174	Highly Destabilizing	0.998	D	0.859	deleterious	D	0.56141621	None	None	N
L/R	0.9826	likely_pathogenic	0.9878	pathogenic	-2.106	Highly Destabilizing	0.998	D	0.862	deleterious	D	0.56141621	None	None	N
L/S	0.9906	likely_pathogenic	0.9934	pathogenic	-2.995	Highly Destabilizing	0.983	D	0.822	deleterious	None	None	None	None	N
L/T	0.9729	likely_pathogenic	0.9802	pathogenic	-2.518	Highly Destabilizing	0.992	D	0.77	deleterious	None	None	None	None	N
L/V	0.2586	likely_benign	0.2774	benign	-1.13	Destabilizing	0.989	D	0.623	neutral	D	0.541537528	None	None	N
L/W	0.9608	likely_pathogenic	0.9729	pathogenic	-1.827	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/Y	0.9662	likely_pathogenic	0.9729	pathogenic	-1.62	Destabilizing	1.0	D	0.768	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.