TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8849	26770;26771;26772	chr2:178714113;178714112;178714111	chr2:179578840;179578839;179578838
N2AB	8532	25819;25820;25821	chr2:178714113;178714112;178714111	chr2:179578840;179578839;179578838
N2A	7605	23038;23039;23040	chr2:178714113;178714112;178714111	chr2:179578840;179578839;179578838
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-74
• Domain position: 20
• Structural Position: 30
• 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/F	None	None	0.64	N	0.446	0.176	0.514866526686	gnomAD-4.0.0	1.20035E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31254E-06	0	0
L/W	None	None	1.0	D	0.867	0.764	0.893513305282	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	0.7804	likely_pathogenic	0.796	pathogenic	-2.658	Highly Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
L/C	0.8821	likely_pathogenic	0.8909	pathogenic	-1.95	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/D	0.9964	likely_pathogenic	0.9973	pathogenic	-3.212	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/E	0.9725	likely_pathogenic	0.9779	pathogenic	-2.904	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/F	0.1348	likely_benign	0.1443	benign	-1.533	Destabilizing	0.64	D	0.446	neutral	N	0.510721402	None	None	N
L/G	0.9682	likely_pathogenic	0.9713	pathogenic	-3.277	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/H	0.9178	likely_pathogenic	0.9342	pathogenic	-2.867	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/I	0.1279	likely_benign	0.1294	benign	-0.813	Destabilizing	0.997	D	0.647	neutral	None	None	None	None	N
L/K	0.9524	likely_pathogenic	0.9614	pathogenic	-1.998	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/M	0.1355	likely_benign	0.1414	benign	-0.916	Destabilizing	1.0	D	0.755	deleterious	D	0.556432163	None	None	N
L/N	0.9841	likely_pathogenic	0.9869	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/P	0.9863	likely_pathogenic	0.9875	pathogenic	-1.416	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/Q	0.8861	likely_pathogenic	0.9091	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/R	0.9086	likely_pathogenic	0.9252	pathogenic	-1.997	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/S	0.9403	likely_pathogenic	0.9515	pathogenic	-3.246	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.639364946	None	None	N
L/T	0.8351	likely_pathogenic	0.8481	pathogenic	-2.768	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/V	0.1602	likely_benign	0.1607	benign	-1.416	Destabilizing	0.996	D	0.684	prob.neutral	D	0.570099517	None	None	N
L/W	0.5144	ambiguous	0.5728	pathogenic	-1.953	Destabilizing	1.0	D	0.867	deleterious	D	0.602218602	None	None	N
L/Y	0.722	likely_pathogenic	0.7645	pathogenic	-1.687	Destabilizing	0.998	D	0.843	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.