TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9900	29923;29924;29925	chr2:178704774;178704773;178704772	chr2:179569501;179569500;179569499
N2AB	9583	28972;28973;28974	chr2:178704774;178704773;178704772	chr2:179569501;179569500;179569499
N2A	8656	26191;26192;26193	chr2:178704774;178704773;178704772	chr2:179569501;179569500;179569499
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-84
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1442
• Predicted PPI site: I

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
V/A	None	None	0.892	None	0.506	0.431	0.672779776643	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	rs2075588711	None	0.025	None	0.269	0.124	0.422040124859	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs2075588711	None	0.025	None	0.269	0.124	0.422040124859	gnomAD-4.0.0	6.44375E-06	None	None	None	None	I	None	6.78702E-05	0	None	0	0	None	0	0	0	0	2.85649E-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
V/A	0.9606	likely_pathogenic	0.9492	pathogenic	-1.82	Destabilizing	0.892	D	0.506	neutral	None	None	None	None	I
V/C	0.9903	likely_pathogenic	0.9903	pathogenic	-1.029	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
V/D	0.9984	likely_pathogenic	0.9977	pathogenic	-2.021	Highly Destabilizing	0.994	D	0.705	prob.neutral	None	None	None	None	I
V/E	0.9937	likely_pathogenic	0.9901	pathogenic	-1.954	Destabilizing	0.996	D	0.648	neutral	None	None	None	None	I
V/F	0.9312	likely_pathogenic	0.918	pathogenic	-1.301	Destabilizing	0.967	D	0.644	neutral	None	None	None	None	I
V/G	0.9858	likely_pathogenic	0.9784	pathogenic	-2.209	Highly Destabilizing	0.983	D	0.702	prob.neutral	None	None	None	None	I
V/H	0.9988	likely_pathogenic	0.9982	pathogenic	-1.928	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
V/I	0.1084	likely_benign	0.1304	benign	-0.804	Destabilizing	0.025	N	0.269	neutral	None	None	None	None	I
V/K	0.995	likely_pathogenic	0.9915	pathogenic	-1.69	Destabilizing	0.987	D	0.651	neutral	None	None	None	None	I
V/L	0.8007	likely_pathogenic	0.816	pathogenic	-0.804	Destabilizing	0.369	N	0.437	neutral	None	None	None	None	I
V/M	0.8267	likely_pathogenic	0.8291	pathogenic	-0.504	Destabilizing	0.975	D	0.651	neutral	None	None	None	None	I
V/N	0.9941	likely_pathogenic	0.994	pathogenic	-1.508	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	I
V/P	0.9948	likely_pathogenic	0.9932	pathogenic	-1.112	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
V/Q	0.9949	likely_pathogenic	0.9913	pathogenic	-1.581	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	I
V/R	0.9914	likely_pathogenic	0.9847	pathogenic	-1.242	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	I
V/S	0.9865	likely_pathogenic	0.9845	pathogenic	-1.988	Destabilizing	0.987	D	0.665	neutral	None	None	None	None	I
V/T	0.9534	likely_pathogenic	0.9496	pathogenic	-1.811	Destabilizing	0.916	D	0.561	neutral	None	None	None	None	I
V/W	0.9993	likely_pathogenic	0.9989	pathogenic	-1.651	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
V/Y	0.9942	likely_pathogenic	0.9921	pathogenic	-1.35	Destabilizing	0.987	D	0.661	neutral	None	None	None	None	I

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.