TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30692	92299;92300;92301	chr2:178549648;178549647;178549646	chr2:179414375;179414374;179414373
N2AB	29051	87376;87377;87378	chr2:178549648;178549647;178549646	chr2:179414375;179414374;179414373
N2A	28124	84595;84596;84597	chr2:178549648;178549647;178549646	chr2:179414375;179414374;179414373
N2B	21627	65104;65105;65106	chr2:178549648;178549647;178549646	chr2:179414375;179414374;179414373
Novex-1	21752	65479;65480;65481	chr2:178549648;178549647;178549646	chr2:179414375;179414374;179414373
Novex-2	21819	65680;65681;65682	chr2:178549648;178549647;178549646	chr2:179414375;179414374;179414373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-111
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.0746
• 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
F/L	None	None	0.999	D	0.669	0.553	0.475895305069	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8585E-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
F/A	0.9969	likely_pathogenic	0.997	pathogenic	-2.194	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
F/C	0.9674	likely_pathogenic	0.9687	pathogenic	-1.375	Destabilizing	1.0	D	0.844	deleterious	D	0.561950328	None	None	N
F/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.367	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
F/E	0.9998	likely_pathogenic	0.9998	pathogenic	-3.125	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
F/G	0.9984	likely_pathogenic	0.9984	pathogenic	-2.645	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
F/H	0.9972	likely_pathogenic	0.997	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
F/I	0.8775	likely_pathogenic	0.9007	pathogenic	-0.712	Destabilizing	1.0	D	0.772	deleterious	N	0.512923347	None	None	N
F/K	0.9998	likely_pathogenic	0.9998	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
F/L	0.9906	likely_pathogenic	0.9919	pathogenic	-0.712	Destabilizing	0.999	D	0.669	neutral	D	0.53114296	None	None	N
F/M	0.9596	likely_pathogenic	0.9623	pathogenic	-0.51	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
F/N	0.9991	likely_pathogenic	0.999	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-1.221	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
F/Q	0.9995	likely_pathogenic	0.9995	pathogenic	-2.634	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
F/R	0.9993	likely_pathogenic	0.9993	pathogenic	-2.174	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
F/S	0.9983	likely_pathogenic	0.9984	pathogenic	-3.26	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.561950328	None	None	N
F/T	0.998	likely_pathogenic	0.9982	pathogenic	-2.887	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
F/V	0.8921	likely_pathogenic	0.9127	pathogenic	-1.221	Destabilizing	1.0	D	0.756	deleterious	N	0.513071023	None	None	N
F/W	0.9454	likely_pathogenic	0.948	pathogenic	-0.429	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
F/Y	0.7347	likely_pathogenic	0.7521	pathogenic	-0.754	Destabilizing	0.999	D	0.59	neutral	N	0.518549342	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.