TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26205	78838;78839;78840	chr2:178567519;178567518;178567517	chr2:179432246;179432245;179432244
N2AB	24564	73915;73916;73917	chr2:178567519;178567518;178567517	chr2:179432246;179432245;179432244
N2A	23637	71134;71135;71136	chr2:178567519;178567518;178567517	chr2:179432246;179432245;179432244
N2B	17140	51643;51644;51645	chr2:178567519;178567518;178567517	chr2:179432246;179432245;179432244
Novex-1	17265	52018;52019;52020	chr2:178567519;178567518;178567517	chr2:179432246;179432245;179432244
Novex-2	17332	52219;52220;52221	chr2:178567519;178567518;178567517	chr2:179432246;179432245;179432244
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-137
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.1751
• 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	rs398124456	None	0.939	D	0.459	0.574	0.69793306553	gnomAD-4.0.0	1.59498E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86261E-06	0	0
V/G	None	None	0.997	D	0.687	0.821	0.928572533926	gnomAD-4.0.0	1.59498E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86261E-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
V/A	0.5868	likely_pathogenic	0.5526	ambiguous	-1.787	Destabilizing	0.939	D	0.459	neutral	D	0.531638179	None	None	I
V/C	0.8252	likely_pathogenic	0.7991	pathogenic	-1.35	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
V/D	0.9757	likely_pathogenic	0.9763	pathogenic	-1.972	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	I
V/E	0.9136	likely_pathogenic	0.9122	pathogenic	-1.83	Destabilizing	0.997	D	0.643	neutral	D	0.559045899	None	None	I
V/F	0.46	ambiguous	0.4708	ambiguous	-1.115	Destabilizing	0.986	D	0.626	neutral	None	None	None	None	I
V/G	0.7783	likely_pathogenic	0.7642	pathogenic	-2.261	Highly Destabilizing	0.997	D	0.687	prob.neutral	D	0.538219392	None	None	I
V/H	0.9537	likely_pathogenic	0.9527	pathogenic	-1.98	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
V/I	0.0846	likely_benign	0.0801	benign	-0.516	Destabilizing	0.046	N	0.227	neutral	N	0.503297421	None	None	I
V/K	0.8799	likely_pathogenic	0.8811	pathogenic	-1.55	Destabilizing	0.993	D	0.645	neutral	None	None	None	None	I
V/L	0.2718	likely_benign	0.2529	benign	-0.516	Destabilizing	0.046	N	0.262	neutral	N	0.515845495	None	None	I
V/M	0.3155	likely_benign	0.3105	benign	-0.5	Destabilizing	0.986	D	0.563	neutral	None	None	None	None	I
V/N	0.9257	likely_pathogenic	0.9185	pathogenic	-1.642	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
V/P	0.9889	likely_pathogenic	0.9885	pathogenic	-0.908	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	I
V/Q	0.8684	likely_pathogenic	0.8653	pathogenic	-1.59	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	I
V/R	0.8448	likely_pathogenic	0.8472	pathogenic	-1.276	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
V/S	0.8278	likely_pathogenic	0.8095	pathogenic	-2.263	Highly Destabilizing	0.993	D	0.628	neutral	None	None	None	None	I
V/T	0.6164	likely_pathogenic	0.5951	pathogenic	-1.985	Destabilizing	0.953	D	0.557	neutral	None	None	None	None	I
V/W	0.9645	likely_pathogenic	0.9619	pathogenic	-1.544	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
V/Y	0.8851	likely_pathogenic	0.8825	pathogenic	-1.162	Destabilizing	0.998	D	0.595	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.