TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25568	76927;76928;76929	chr2:178569430;178569429;178569428	chr2:179434157;179434156;179434155
N2AB	23927	72004;72005;72006	chr2:178569430;178569429;178569428	chr2:179434157;179434156;179434155
N2A	23000	69223;69224;69225	chr2:178569430;178569429;178569428	chr2:179434157;179434156;179434155
N2B	16503	49732;49733;49734	chr2:178569430;178569429;178569428	chr2:179434157;179434156;179434155
Novex-1	16628	50107;50108;50109	chr2:178569430;178569429;178569428	chr2:179434157;179434156;179434155
Novex-2	16695	50308;50309;50310	chr2:178569430;178569429;178569428	chr2:179434157;179434156;179434155
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-135
• Domain position: 55
• Structural Position: 140
• Q(SASA): 0.1695
• 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/P	None	None	0.994	N	0.855	0.778	0.87689326119	gnomAD-4.0.0	1.36885E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79927E-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	0.6318	likely_pathogenic	0.6497	pathogenic	-2.45	Highly Destabilizing	0.916	D	0.688	prob.neutral	None	None	None	None	N
L/C	0.7037	likely_pathogenic	0.7296	pathogenic	-1.826	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
L/D	0.9803	likely_pathogenic	0.9818	pathogenic	-2.59	Highly Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
L/E	0.8787	likely_pathogenic	0.8861	pathogenic	-2.486	Highly Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	N
L/F	0.299	likely_benign	0.3065	benign	-1.584	Destabilizing	0.967	D	0.733	prob.delet.	N	0.484903025	None	None	N
L/G	0.9456	likely_pathogenic	0.9503	pathogenic	-2.891	Highly Destabilizing	0.987	D	0.861	deleterious	None	None	None	None	N
L/H	0.7379	likely_pathogenic	0.7449	pathogenic	-2.15	Highly Destabilizing	0.999	D	0.835	deleterious	N	0.495206345	None	None	N
L/I	0.0824	likely_benign	0.0797	benign	-1.229	Destabilizing	0.011	N	0.294	neutral	N	0.316648877	None	None	N
L/K	0.8431	likely_pathogenic	0.8468	pathogenic	-1.935	Destabilizing	0.987	D	0.847	deleterious	None	None	None	None	N
L/M	0.147	likely_benign	0.1498	benign	-1.097	Destabilizing	0.975	D	0.69	prob.neutral	None	None	None	None	N
L/N	0.8993	likely_pathogenic	0.9011	pathogenic	-1.982	Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
L/P	0.9815	likely_pathogenic	0.9821	pathogenic	-1.612	Destabilizing	0.994	D	0.855	deleterious	N	0.495206345	None	None	N
L/Q	0.671	likely_pathogenic	0.6873	pathogenic	-2.06	Highly Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
L/R	0.7672	likely_pathogenic	0.7813	pathogenic	-1.367	Destabilizing	0.994	D	0.833	deleterious	N	0.495206345	None	None	N
L/S	0.8039	likely_pathogenic	0.8117	pathogenic	-2.64	Highly Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
L/T	0.5711	likely_pathogenic	0.5952	pathogenic	-2.412	Highly Destabilizing	0.975	D	0.77	deleterious	None	None	None	None	N
L/V	0.1041	likely_benign	0.1069	benign	-1.612	Destabilizing	0.369	N	0.503	neutral	N	0.409557117	None	None	N
L/W	0.6674	likely_pathogenic	0.6886	pathogenic	-1.816	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
L/Y	0.737	likely_pathogenic	0.759	pathogenic	-1.602	Destabilizing	0.987	D	0.755	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.