TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32379	97360;97361;97362	chr2:178542719;178542718;178542717	chr2:179407446;179407445;179407444
N2AB	30738	92437;92438;92439	chr2:178542719;178542718;178542717	chr2:179407446;179407445;179407444
N2A	29811	89656;89657;89658	chr2:178542719;178542718;178542717	chr2:179407446;179407445;179407444
N2B	23314	70165;70166;70167	chr2:178542719;178542718;178542717	chr2:179407446;179407445;179407444
Novex-1	23439	70540;70541;70542	chr2:178542719;178542718;178542717	chr2:179407446;179407445;179407444
Novex-2	23506	70741;70742;70743	chr2:178542719;178542718;178542717	chr2:179407446;179407445;179407444
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-154
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.091
• 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/F	rs1361697291	-1.724	1.0	N	0.841	0.387	0.406945738958	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.29634E-04	0
L/F	rs1361697291	-1.724	1.0	N	0.841	0.387	0.406945738958	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1361697291	-1.724	1.0	N	0.841	0.387	0.406945738958	gnomAD-4.0.0	6.08986E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.2296E-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	0.8701	likely_pathogenic	0.8077	pathogenic	-2.468	Highly Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
L/C	0.8634	likely_pathogenic	0.8296	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9991	pathogenic	-2.636	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/E	0.995	likely_pathogenic	0.9919	pathogenic	-2.388	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/F	0.6195	likely_pathogenic	0.4845	ambiguous	-1.476	Destabilizing	1.0	D	0.841	deleterious	N	0.453071995	None	None	N
L/G	0.9855	likely_pathogenic	0.9762	pathogenic	-3.047	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/H	0.9893	likely_pathogenic	0.9831	pathogenic	-2.544	Highly Destabilizing	1.0	D	0.853	deleterious	N	0.472697187	None	None	N
L/I	0.1464	likely_benign	0.1234	benign	-0.788	Destabilizing	0.999	D	0.714	prob.delet.	N	0.452090733	None	None	N
L/K	0.9911	likely_pathogenic	0.987	pathogenic	-1.807	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/M	0.2312	likely_benign	0.2004	benign	-0.932	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/N	0.9957	likely_pathogenic	0.9939	pathogenic	-2.207	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/P	0.9937	likely_pathogenic	0.9903	pathogenic	-1.328	Destabilizing	1.0	D	0.885	deleterious	N	0.472697187	None	None	N
L/Q	0.9774	likely_pathogenic	0.9662	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/R	0.9799	likely_pathogenic	0.9687	pathogenic	-1.637	Destabilizing	1.0	D	0.886	deleterious	N	0.472697187	None	None	N
L/S	0.9887	likely_pathogenic	0.9801	pathogenic	-2.97	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/T	0.9319	likely_pathogenic	0.8962	pathogenic	-2.557	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/V	0.1516	likely_benign	0.1268	benign	-1.328	Destabilizing	0.999	D	0.738	prob.delet.	N	0.446279482	None	None	N
L/W	0.9472	likely_pathogenic	0.9045	pathogenic	-1.84	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/Y	0.9657	likely_pathogenic	0.9428	pathogenic	-1.54	Destabilizing	1.0	D	0.86	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.