TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32267	97024;97025;97026	chr2:178543174;178543173;178543172	chr2:179407901;179407900;179407899
N2AB	30626	92101;92102;92103	chr2:178543174;178543173;178543172	chr2:179407901;179407900;179407899
N2A	29699	89320;89321;89322	chr2:178543174;178543173;178543172	chr2:179407901;179407900;179407899
N2B	23202	69829;69830;69831	chr2:178543174;178543173;178543172	chr2:179407901;179407900;179407899
Novex-1	23327	70204;70205;70206	chr2:178543174;178543173;178543172	chr2:179407901;179407900;179407899
Novex-2	23394	70405;70406;70407	chr2:178543174;178543173;178543172	chr2:179407901;179407900;179407899
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-123
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.123
• 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
L/S	None	None	1.0	D	0.845	0.876	0.924462296912	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9073	likely_pathogenic	0.9037	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/C	0.8732	likely_pathogenic	0.8494	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/D	0.9985	likely_pathogenic	0.9986	pathogenic	-1.514	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/E	0.9897	likely_pathogenic	0.9904	pathogenic	-1.385	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/F	0.7211	likely_pathogenic	0.7291	pathogenic	-1.664	Destabilizing	1.0	D	0.871	deleterious	D	0.629919379	None	None	N
L/G	0.9722	likely_pathogenic	0.9741	pathogenic	-2.799	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/H	0.9791	likely_pathogenic	0.9798	pathogenic	-1.951	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/I	0.3926	ambiguous	0.3696	ambiguous	-1.096	Destabilizing	0.991	D	0.823	deleterious	D	0.599889776	None	None	N
L/K	0.9749	likely_pathogenic	0.9778	pathogenic	-1.539	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
L/M	0.4012	ambiguous	0.4035	ambiguous	-1.139	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/N	0.9895	likely_pathogenic	0.9898	pathogenic	-1.62	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/P	0.9813	likely_pathogenic	0.9817	pathogenic	-1.487	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/Q	0.9461	likely_pathogenic	0.9454	pathogenic	-1.633	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/R	0.9461	likely_pathogenic	0.9478	pathogenic	-1.114	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/S	0.9835	likely_pathogenic	0.9821	pathogenic	-2.494	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.646745957	None	None	N
L/T	0.9357	likely_pathogenic	0.9359	pathogenic	-2.211	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/V	0.3816	ambiguous	0.3429	ambiguous	-1.487	Destabilizing	0.993	D	0.833	deleterious	D	0.564188291	None	None	N
L/W	0.9443	likely_pathogenic	0.9449	pathogenic	-1.729	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/Y	0.972	likely_pathogenic	0.9728	pathogenic	-1.498	Destabilizing	0.999	D	0.826	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.