TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24262	73009;73010;73011	chr2:178573348;178573347;178573346	chr2:179438075;179438074;179438073
N2AB	22621	68086;68087;68088	chr2:178573348;178573347;178573346	chr2:179438075;179438074;179438073
N2A	21694	65305;65306;65307	chr2:178573348;178573347;178573346	chr2:179438075;179438074;179438073
N2B	15197	45814;45815;45816	chr2:178573348;178573347;178573346	chr2:179438075;179438074;179438073
Novex-1	15322	46189;46190;46191	chr2:178573348;178573347;178573346	chr2:179438075;179438074;179438073
Novex-2	15389	46390;46391;46392	chr2:178573348;178573347;178573346	chr2:179438075;179438074;179438073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-64
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1457
• 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
R/C	rs576976296	-1.584	1.0	N	0.759	0.401	0.613436686781	gnomAD-2.1.1	1.82E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.13E-05	None	0	2.84E-05	0
R/C	rs576976296	-1.584	1.0	N	0.759	0.401	0.613436686781	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	2.07727E-04	0
R/C	rs576976296	-1.584	1.0	N	0.759	0.401	0.613436686781	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/C	rs576976296	-1.584	1.0	N	0.759	0.401	0.613436686781	gnomAD-4.0.0	4.5562E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25303E-06	1.29992E-05	0
R/H	rs372390659	-2.116	0.385	N	0.263	0.264	None	gnomAD-2.1.1	4.09E-05	None	None	None	None	N	None	4.26E-05	0	None	0	0	None	1.84049E-04	None	0	4.74E-05	0
R/H	rs372390659	-2.116	0.385	N	0.263	0.264	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	2.07297E-04	0
R/H	rs372390659	-2.116	0.385	N	0.263	0.264	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/H	rs372390659	-2.116	0.385	N	0.263	0.264	None	gnomAD-4.0.0	2.7327E-05	None	None	None	None	N	None	1.37756E-05	0	None	0	0	None	0	1.75747E-04	2.71316E-05	1.03839E-04	1.69045E-05
R/S	None	None	0.975	N	0.597	0.346	0.350088858571	gnomAD-4.0.0	7.2233E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.30868E-07	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
R/A	0.9613	likely_pathogenic	0.9046	pathogenic	-2.022	Highly Destabilizing	0.953	D	0.517	neutral	None	None	None	None	N
R/C	0.4297	ambiguous	0.2803	benign	-1.822	Destabilizing	1.0	D	0.759	deleterious	N	0.48585587	None	None	N
R/D	0.9954	likely_pathogenic	0.9847	pathogenic	-0.842	Destabilizing	0.986	D	0.687	prob.neutral	None	None	None	None	N
R/E	0.9475	likely_pathogenic	0.8736	pathogenic	-0.619	Destabilizing	0.953	D	0.444	neutral	None	None	None	None	N
R/F	0.9408	likely_pathogenic	0.8461	pathogenic	-1.219	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
R/G	0.9361	likely_pathogenic	0.835	pathogenic	-2.386	Highly Destabilizing	0.975	D	0.625	neutral	N	0.52181089	None	None	N
R/H	0.2335	likely_benign	0.1441	benign	-2.067	Highly Destabilizing	0.385	N	0.263	neutral	N	0.507176129	None	None	N
R/I	0.9048	likely_pathogenic	0.7937	pathogenic	-0.964	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
R/K	0.2053	likely_benign	0.1645	benign	-1.213	Destabilizing	0.893	D	0.477	neutral	None	None	None	None	N
R/L	0.7807	likely_pathogenic	0.6205	pathogenic	-0.964	Destabilizing	0.993	D	0.647	neutral	N	0.501629493	None	None	N
R/M	0.8559	likely_pathogenic	0.7366	pathogenic	-1.4	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
R/N	0.9716	likely_pathogenic	0.9282	pathogenic	-1.233	Destabilizing	0.953	D	0.483	neutral	None	None	None	None	N
R/P	0.9985	likely_pathogenic	0.9954	pathogenic	-1.306	Destabilizing	0.999	D	0.754	deleterious	D	0.54477699	None	None	N
R/Q	0.3024	likely_benign	0.1993	benign	-1.156	Destabilizing	0.986	D	0.528	neutral	None	None	None	None	N
R/S	0.9778	likely_pathogenic	0.9387	pathogenic	-2.215	Highly Destabilizing	0.975	D	0.597	neutral	N	0.489966792	None	None	N
R/T	0.9528	likely_pathogenic	0.8851	pathogenic	-1.769	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
R/V	0.9329	likely_pathogenic	0.8523	pathogenic	-1.306	Destabilizing	0.993	D	0.786	deleterious	None	None	None	None	N
R/W	0.6158	likely_pathogenic	0.3924	ambiguous	-0.653	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
R/Y	0.8377	likely_pathogenic	0.6626	pathogenic	-0.544	Destabilizing	0.973	D	0.751	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.