TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23213	69862;69863;69864	chr2:178576607;178576606;178576605	chr2:179441334;179441333;179441332
N2AB	21572	64939;64940;64941	chr2:178576607;178576606;178576605	chr2:179441334;179441333;179441332
N2A	20645	62158;62159;62160	chr2:178576607;178576606;178576605	chr2:179441334;179441333;179441332
N2B	14148	42667;42668;42669	chr2:178576607;178576606;178576605	chr2:179441334;179441333;179441332
Novex-1	14273	43042;43043;43044	chr2:178576607;178576606;178576605	chr2:179441334;179441333;179441332
Novex-2	14340	43243;43244;43245	chr2:178576607;178576606;178576605	chr2:179441334;179441333;179441332
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: Fn3-56
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1538
• 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	rs1335495074	-1.707	1.0	D	0.825	0.536	0.720252389933	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
R/C	rs1335495074	-1.707	1.0	D	0.825	0.536	0.720252389933	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs1335495074	-1.707	1.0	D	0.825	0.536	0.720252389933	gnomAD-4.0.0	9.91679E-06	None	None	None	None	N	None	0	5.00233E-05	None	0	2.23025E-05	None	0	0	1.01727E-05	0	0
R/H	rs374883884	-2.313	1.0	D	0.817	0.599	None	gnomAD-2.1.1	7.86E-05	None	None	None	None	N	None	4.13E-05	5.66E-05	None	9.67E-05	7.19646E-04	None	9.8E-05	None	0	7.83E-06	0
R/H	rs374883884	-2.313	1.0	D	0.817	0.599	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	N	None	4.83E-05	3.92773E-04	0	0	7.75494E-04	None	0	0	0	2.07211E-04	0
R/H	rs374883884	-2.313	1.0	D	0.817	0.599	None	gnomAD-4.0.0	2.6029E-05	None	None	None	None	N	None	6.66507E-05	1.4997E-04	None	3.37929E-05	2.45437E-04	None	3.12402E-05	0	6.7818E-06	4.39252E-05	3.20195E-05
R/P	rs374883884	-1.342	1.0	D	0.801	0.609	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/P	rs374883884	-1.342	1.0	D	0.801	0.609	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/P	rs374883884	-1.342	1.0	D	0.801	0.609	None	gnomAD-4.0.0	1.85935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54316E-06	0	0
R/S	rs1335495074	-2.122	1.0	N	0.738	0.493	0.54347143358	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
R/S	rs1335495074	-2.122	1.0	N	0.738	0.493	0.54347143358	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/S	rs1335495074	-2.122	1.0	N	0.738	0.493	0.54347143358	gnomAD-4.0.0	6.5767E-06	None	None	None	None	N	None	2.41231E-05	0	None	0	0	None	0	0	0	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	0.9373	likely_pathogenic	0.9461	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
R/C	0.3647	ambiguous	0.3781	ambiguous	-1.935	Destabilizing	1.0	D	0.825	deleterious	D	0.538272985	None	None	N
R/D	0.9964	likely_pathogenic	0.9966	pathogenic	-0.751	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
R/E	0.9339	likely_pathogenic	0.9397	pathogenic	-0.55	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
R/F	0.9426	likely_pathogenic	0.9467	pathogenic	-1.401	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
R/G	0.946	likely_pathogenic	0.9534	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.735	prob.delet.	D	0.55612375	None	None	N
R/H	0.2269	likely_benign	0.2196	benign	-2.186	Highly Destabilizing	1.0	D	0.817	deleterious	D	0.533500045	None	None	N
R/I	0.8667	likely_pathogenic	0.8684	pathogenic	-1.028	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
R/K	0.4248	ambiguous	0.3892	ambiguous	-1.373	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
R/L	0.7592	likely_pathogenic	0.7801	pathogenic	-1.028	Destabilizing	1.0	D	0.735	prob.delet.	N	0.511774939	None	None	N
R/M	0.8613	likely_pathogenic	0.8683	pathogenic	-1.482	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
R/N	0.9808	likely_pathogenic	0.9811	pathogenic	-1.189	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
R/P	0.9986	likely_pathogenic	0.9986	pathogenic	-1.34	Destabilizing	1.0	D	0.801	deleterious	D	0.556630729	None	None	N
R/Q	0.2506	likely_benign	0.2665	benign	-1.182	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
R/S	0.9604	likely_pathogenic	0.9631	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.738	prob.delet.	N	0.516619877	None	None	N
R/T	0.9222	likely_pathogenic	0.9258	pathogenic	-1.781	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
R/V	0.8855	likely_pathogenic	0.8899	pathogenic	-1.34	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
R/W	0.5496	ambiguous	0.5673	pathogenic	-0.855	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
R/Y	0.8748	likely_pathogenic	0.882	pathogenic	-0.698	Destabilizing	1.0	D	0.829	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.