TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32946	99061;99062;99063	chr2:178539099;178539098;178539097	chr2:179403826;179403825;179403824
N2AB	31305	94138;94139;94140	chr2:178539099;178539098;178539097	chr2:179403826;179403825;179403824
N2A	30378	91357;91358;91359	chr2:178539099;178539098;178539097	chr2:179403826;179403825;179403824
N2B	23881	71866;71867;71868	chr2:178539099;178539098;178539097	chr2:179403826;179403825;179403824
Novex-1	24006	72241;72242;72243	chr2:178539099;178539098;178539097	chr2:179403826;179403825;179403824
Novex-2	24073	72442;72443;72444	chr2:178539099;178539098;178539097	chr2:179403826;179403825;179403824
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-128
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.2633
• 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/G	None	None	1.0	N	0.685	0.47	0.514416127146	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.9136	likely_pathogenic	0.9055	pathogenic	-0.767	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
R/C	0.5687	likely_pathogenic	0.5381	ambiguous	-0.823	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
R/D	0.979	likely_pathogenic	0.9791	pathogenic	-0.03	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
R/E	0.8761	likely_pathogenic	0.861	pathogenic	0.14	Stabilizing	0.999	D	0.672	neutral	None	None	None	None	N
R/F	0.9345	likely_pathogenic	0.9271	pathogenic	-0.338	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/G	0.905	likely_pathogenic	0.8978	pathogenic	-1.119	Destabilizing	1.0	D	0.685	prob.neutral	N	0.490638355	None	None	N
R/H	0.3836	ambiguous	0.4041	ambiguous	-1.336	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
R/I	0.7126	likely_pathogenic	0.6758	pathogenic	0.193	Stabilizing	1.0	D	0.768	deleterious	N	0.511131542	None	None	N
R/K	0.2633	likely_benign	0.3141	benign	-0.705	Destabilizing	0.997	D	0.507	neutral	N	0.440770167	None	None	N
R/L	0.6068	likely_pathogenic	0.6084	pathogenic	0.193	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
R/M	0.7648	likely_pathogenic	0.7598	pathogenic	-0.369	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
R/N	0.951	likely_pathogenic	0.9511	pathogenic	-0.422	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
R/P	0.8544	likely_pathogenic	0.854	pathogenic	-0.106	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/Q	0.2984	likely_benign	0.3028	benign	-0.425	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/S	0.9499	likely_pathogenic	0.9458	pathogenic	-1.155	Destabilizing	1.0	D	0.737	prob.delet.	N	0.49063884	None	None	N
R/T	0.7859	likely_pathogenic	0.7829	pathogenic	-0.78	Destabilizing	1.0	D	0.729	prob.delet.	N	0.46272152	None	None	N
R/V	0.7904	likely_pathogenic	0.784	pathogenic	-0.106	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
R/W	0.6022	likely_pathogenic	0.563	ambiguous	0.016	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
R/Y	0.8622	likely_pathogenic	0.8497	pathogenic	0.272	Stabilizing	1.0	D	0.762	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.