TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23077	69454;69455;69456	chr2:178577106;178577105;178577104	chr2:179441833;179441832;179441831
N2AB	21436	64531;64532;64533	chr2:178577106;178577105;178577104	chr2:179441833;179441832;179441831
N2A	20509	61750;61751;61752	chr2:178577106;178577105;178577104	chr2:179441833;179441832;179441831
N2B	14012	42259;42260;42261	chr2:178577106;178577105;178577104	chr2:179441833;179441832;179441831
Novex-1	14137	42634;42635;42636	chr2:178577106;178577105;178577104	chr2:179441833;179441832;179441831
Novex-2	14204	42835;42836;42837	chr2:178577106;178577105;178577104	chr2:179441833;179441832;179441831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-55
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0795
• 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/F	rs529270980	-1.827	0.988	N	0.784	0.444	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24028E-04	0	None	0	0	None	0	None	0	0	0
L/F	rs529270980	-1.827	0.988	N	0.784	0.444	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs529270980	-1.827	0.988	N	0.784	0.444	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
L/F	rs529270980	-1.827	0.988	N	0.784	0.444	None	gnomAD-4.0.0	1.05378E-05	None	None	None	None	N	None	1.46729E-04	0	None	0	0	None	0	0	5.08672E-06	0	0
L/I	None	None	0.067	N	0.368	0.114	0.283371740733	gnomAD-4.0.0	6.84378E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9963E-07	0	0
L/P	rs772742230	-2.22	0.998	N	0.893	0.633	0.86346069705	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/P	rs772742230	-2.22	0.998	N	0.893	0.633	0.86346069705	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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
L/A	0.8954	likely_pathogenic	0.8688	pathogenic	-2.958	Highly Destabilizing	0.968	D	0.686	prob.neutral	None	None	None	None	N
L/C	0.8953	likely_pathogenic	0.8736	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.735	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
L/E	0.9974	likely_pathogenic	0.9966	pathogenic	-3.407	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
L/F	0.7891	likely_pathogenic	0.7507	pathogenic	-1.779	Destabilizing	0.988	D	0.784	deleterious	N	0.506179078	None	None	N
L/G	0.9934	likely_pathogenic	0.992	pathogenic	-3.579	Highly Destabilizing	0.995	D	0.869	deleterious	None	None	None	None	N
L/H	0.9947	likely_pathogenic	0.9935	pathogenic	-3.196	Highly Destabilizing	0.999	D	0.874	deleterious	N	0.517788873	None	None	N
L/I	0.0975	likely_benign	0.0907	benign	-1.083	Destabilizing	0.067	N	0.368	neutral	N	0.386700821	None	None	N
L/K	0.9964	likely_pathogenic	0.9956	pathogenic	-2.405	Highly Destabilizing	0.995	D	0.869	deleterious	None	None	None	None	N
L/M	0.3432	ambiguous	0.3074	benign	-1.18	Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	N
L/N	0.9984	likely_pathogenic	0.9979	pathogenic	-3.133	Highly Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
L/P	0.9957	likely_pathogenic	0.9955	pathogenic	-1.7	Destabilizing	0.998	D	0.893	deleterious	N	0.506432568	None	None	N
L/Q	0.9908	likely_pathogenic	0.9882	pathogenic	-2.792	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/R	0.9913	likely_pathogenic	0.9897	pathogenic	-2.375	Highly Destabilizing	0.998	D	0.886	deleterious	N	0.517788873	None	None	N
L/S	0.9919	likely_pathogenic	0.9886	pathogenic	-3.708	Highly Destabilizing	0.995	D	0.875	deleterious	None	None	None	None	N
L/T	0.9249	likely_pathogenic	0.9023	pathogenic	-3.214	Highly Destabilizing	0.991	D	0.803	deleterious	None	None	None	None	N
L/V	0.0953	likely_benign	0.0893	benign	-1.7	Destabilizing	0.618	D	0.632	neutral	N	0.36235695	None	None	N
L/W	0.9827	likely_pathogenic	0.9796	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/Y	0.9872	likely_pathogenic	0.983	pathogenic	-1.994	Destabilizing	0.995	D	0.837	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.