TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14566	43921;43922;43923	chr2:178632198;178632197;178632196	chr2:179496925;179496924;179496923
N2AB	12925	38998;38999;39000	chr2:178632198;178632197;178632196	chr2:179496925;179496924;179496923
N2A	11998	36217;36218;36219	chr2:178632198;178632197;178632196	chr2:179496925;179496924;179496923
N2B	5501	16726;16727;16728	chr2:178632198;178632197;178632196	chr2:179496925;179496924;179496923
Novex-1	5626	17101;17102;17103	chr2:178632198;178632197;178632196	chr2:179496925;179496924;179496923
Novex-2	5693	17302;17303;17304	chr2:178632198;178632197;178632196	chr2:179496925;179496924;179496923
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-96
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.0885
• 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
I/L	rs1415295161	None	0.993	D	0.539	0.634	0.711098882349	gnomAD-4.0.0	1.30414E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.53222E-05	0	3.32325E-05

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
I/A	0.9658	likely_pathogenic	0.9615	pathogenic	-2.672	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
I/C	0.9683	likely_pathogenic	0.9664	pathogenic	-1.797	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
I/D	0.9972	likely_pathogenic	0.9976	pathogenic	-3.391	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
I/E	0.9914	likely_pathogenic	0.9924	pathogenic	-3.052	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
I/F	0.3818	ambiguous	0.2777	benign	-1.633	Destabilizing	1.0	D	0.821	deleterious	D	0.648170235	None	None	N
I/G	0.9892	likely_pathogenic	0.9886	pathogenic	-3.291	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
I/H	0.9818	likely_pathogenic	0.9795	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/K	0.9821	likely_pathogenic	0.9824	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
I/L	0.2956	likely_benign	0.2595	benign	-0.796	Destabilizing	0.993	D	0.539	neutral	D	0.686387003	None	None	N
I/M	0.3298	likely_benign	0.2676	benign	-0.996	Destabilizing	1.0	D	0.776	deleterious	D	0.685183746	None	None	N
I/N	0.9574	likely_pathogenic	0.9579	pathogenic	-2.855	Highly Destabilizing	1.0	D	0.898	deleterious	D	0.685183746	None	None	N
I/P	0.9937	likely_pathogenic	0.9952	pathogenic	-1.415	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
I/Q	0.9849	likely_pathogenic	0.9849	pathogenic	-2.433	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
I/R	0.9692	likely_pathogenic	0.9691	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
I/S	0.9689	likely_pathogenic	0.9697	pathogenic	-3.348	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.685183746	None	None	N
I/T	0.9583	likely_pathogenic	0.9516	pathogenic	-2.834	Highly Destabilizing	1.0	D	0.831	deleterious	D	0.685183746	None	None	N
I/V	0.1734	likely_benign	0.159	benign	-1.415	Destabilizing	0.993	D	0.479	neutral	D	0.573254879	None	None	N
I/W	0.9671	likely_pathogenic	0.9518	pathogenic	-1.999	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/Y	0.7888	likely_pathogenic	0.7117	pathogenic	-1.816	Destabilizing	1.0	D	0.837	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.