TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25964	78115;78116;78117	chr2:178568242;178568241;178568240	chr2:179432969;179432968;179432967
N2AB	24323	73192;73193;73194	chr2:178568242;178568241;178568240	chr2:179432969;179432968;179432967
N2A	23396	70411;70412;70413	chr2:178568242;178568241;178568240	chr2:179432969;179432968;179432967
N2B	16899	50920;50921;50922	chr2:178568242;178568241;178568240	chr2:179432969;179432968;179432967
Novex-1	17024	51295;51296;51297	chr2:178568242;178568241;178568240	chr2:179432969;179432968;179432967
Novex-2	17091	51496;51497;51498	chr2:178568242;178568241;178568240	chr2:179432969;179432968;179432967
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: Fn3-76
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1168
• 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	rs745748153	-2.496	0.698	D	0.568	0.428	0.579660715472	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/G	rs745748153	-2.496	0.698	D	0.568	0.428	0.579660715472	gnomAD-4.0.0	3.18347E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86574E-05	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	0.8704	likely_pathogenic	0.862	pathogenic	-2.192	Highly Destabilizing	0.559	D	0.596	neutral	None	None	None	None	N
R/C	0.2696	likely_benign	0.2653	benign	-1.959	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
R/D	0.9887	likely_pathogenic	0.9882	pathogenic	-1.48	Destabilizing	0.956	D	0.621	neutral	None	None	None	None	N
R/E	0.8695	likely_pathogenic	0.8696	pathogenic	-1.262	Destabilizing	0.754	D	0.561	neutral	None	None	None	None	N
R/F	0.9355	likely_pathogenic	0.9312	pathogenic	-1.186	Destabilizing	0.978	D	0.741	deleterious	None	None	None	None	N
R/G	0.8637	likely_pathogenic	0.8552	pathogenic	-2.493	Highly Destabilizing	0.698	D	0.568	neutral	D	0.554477909	None	None	N
R/H	0.2686	likely_benign	0.259	benign	-2.237	Highly Destabilizing	0.993	D	0.587	neutral	None	None	None	None	N
R/I	0.7376	likely_pathogenic	0.7179	pathogenic	-1.293	Destabilizing	0.97	D	0.738	prob.delet.	D	0.522384002	None	None	N
R/K	0.1798	likely_benign	0.1484	benign	-1.431	Destabilizing	0.014	N	0.355	neutral	N	0.485032949	None	None	N
R/L	0.6802	likely_pathogenic	0.6586	pathogenic	-1.293	Destabilizing	0.86	D	0.573	neutral	None	None	None	None	N
R/M	0.6944	likely_pathogenic	0.6669	pathogenic	-1.796	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	N
R/N	0.9452	likely_pathogenic	0.9404	pathogenic	-1.701	Destabilizing	0.86	D	0.547	neutral	None	None	None	None	N
R/P	0.9975	likely_pathogenic	0.9976	pathogenic	-1.588	Destabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	N
R/Q	0.194	likely_benign	0.1938	benign	-1.412	Destabilizing	0.956	D	0.569	neutral	None	None	None	None	N
R/S	0.9021	likely_pathogenic	0.8979	pathogenic	-2.375	Highly Destabilizing	0.058	N	0.463	neutral	N	0.514974035	None	None	N
R/T	0.8145	likely_pathogenic	0.8126	pathogenic	-1.97	Destabilizing	0.698	D	0.551	neutral	N	0.497630249	None	None	N
R/V	0.7828	likely_pathogenic	0.7673	pathogenic	-1.588	Destabilizing	0.956	D	0.668	neutral	None	None	None	None	N
R/W	0.671	likely_pathogenic	0.6682	pathogenic	-0.819	Destabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
R/Y	0.8408	likely_pathogenic	0.8309	pathogenic	-0.783	Destabilizing	0.993	D	0.709	prob.delet.	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.