TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32034	96325;96326;96327	chr2:178544044;178544043;178544042	chr2:179408771;179408770;179408769
N2AB	30393	91402;91403;91404	chr2:178544044;178544043;178544042	chr2:179408771;179408770;179408769
N2A	29466	88621;88622;88623	chr2:178544044;178544043;178544042	chr2:179408771;179408770;179408769
N2B	22969	69130;69131;69132	chr2:178544044;178544043;178544042	chr2:179408771;179408770;179408769
Novex-1	23094	69505;69506;69507	chr2:178544044;178544043;178544042	chr2:179408771;179408770;179408769
Novex-2	23161	69706;69707;69708	chr2:178544044;178544043;178544042	chr2:179408771;179408770;179408769
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-153
• Domain position: 18
• Structural Position: 30
• Q(SASA): 0.2406
• 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	rs879175066	None	0.999	N	0.794	0.308	0.516491959214	gnomAD-4.0.0	6.36618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14354E-05	0	0
L/S	rs778697335	-3.173	0.999	D	0.873	0.803	0.913936636291	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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	0.9669	likely_pathogenic	0.9604	pathogenic	-2.097	Highly Destabilizing	0.997	D	0.769	deleterious	None	None	None	None	N
L/C	0.932	likely_pathogenic	0.9198	pathogenic	-1.53	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9994	pathogenic	-2.682	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/E	0.9971	likely_pathogenic	0.9964	pathogenic	-2.436	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/F	0.599	likely_pathogenic	0.5537	ambiguous	-1.453	Destabilizing	0.999	D	0.794	deleterious	N	0.520148962	None	None	N
L/G	0.9941	likely_pathogenic	0.993	pathogenic	-2.545	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/H	0.9921	likely_pathogenic	0.9896	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/I	0.1803	likely_benign	0.1667	benign	-0.77	Destabilizing	0.994	D	0.655	neutral	None	None	None	None	N
L/K	0.9939	likely_pathogenic	0.9929	pathogenic	-1.748	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/M	0.2637	likely_benign	0.2596	benign	-0.868	Destabilizing	0.981	D	0.599	neutral	D	0.549002894	None	None	N
L/N	0.9969	likely_pathogenic	0.9964	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/P	0.9968	likely_pathogenic	0.996	pathogenic	-1.203	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/Q	0.9884	likely_pathogenic	0.9855	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/R	0.9911	likely_pathogenic	0.9886	pathogenic	-1.829	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/S	0.9959	likely_pathogenic	0.9948	pathogenic	-2.785	Highly Destabilizing	0.999	D	0.873	deleterious	D	0.648651532	None	None	N
L/T	0.9838	likely_pathogenic	0.9797	pathogenic	-2.394	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/V	0.2806	likely_benign	0.2553	benign	-1.203	Destabilizing	0.992	D	0.673	neutral	D	0.557794791	None	None	N
L/W	0.9688	likely_pathogenic	0.9563	pathogenic	-1.704	Destabilizing	1.0	D	0.827	deleterious	D	0.632632171	None	None	N
L/Y	0.9651	likely_pathogenic	0.9574	pathogenic	-1.457	Destabilizing	1.0	D	0.799	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.