TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8824	26695;26696;26697	chr2:178714304;178714303;178714302	chr2:179579031;179579030;179579029
N2AB	8507	25744;25745;25746	chr2:178714304;178714303;178714302	chr2:179579031;179579030;179579029
N2A	7580	22963;22964;22965	chr2:178714304;178714303;178714302	chr2:179579031;179579030;179579029
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: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-73
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.2169
• 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/I	rs1322441627	-0.801	0.008	N	0.642	0.141	0.19670166235	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
L/I	rs1322441627	-0.801	0.008	N	0.642	0.141	0.19670166235	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/I	rs1322441627	-0.801	0.008	N	0.642	0.141	0.19670166235	gnomAD-4.0.0	6.57263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46994E-05	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	0.5728	likely_pathogenic	0.7114	pathogenic	-2.726	Highly Destabilizing	0.722	D	0.675	prob.neutral	None	None	None	None	N
L/C	0.6685	likely_pathogenic	0.7888	pathogenic	-2.492	Highly Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
L/D	0.9838	likely_pathogenic	0.9925	pathogenic	-2.579	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
L/E	0.9295	likely_pathogenic	0.9607	pathogenic	-2.297	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/F	0.1907	likely_benign	0.2261	benign	-1.74	Destabilizing	0.879	D	0.794	deleterious	None	None	None	None	N
L/G	0.8833	likely_pathogenic	0.9384	pathogenic	-3.333	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/H	0.8112	likely_pathogenic	0.8922	pathogenic	-2.806	Highly Destabilizing	0.994	D	0.873	deleterious	None	None	None	None	N
L/I	0.072	likely_benign	0.0807	benign	-0.941	Destabilizing	0.008	N	0.642	neutral	N	0.502028476	None	None	N
L/K	0.9151	likely_pathogenic	0.9513	pathogenic	-2.051	Highly Destabilizing	0.971	D	0.857	deleterious	None	None	None	None	N
L/M	0.1471	likely_benign	0.1879	benign	-1.185	Destabilizing	0.685	D	0.775	deleterious	None	None	None	None	N
L/N	0.9033	likely_pathogenic	0.9519	pathogenic	-2.513	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/P	0.9503	likely_pathogenic	0.9753	pathogenic	-1.52	Destabilizing	1.0	D	0.871	deleterious	D	0.545926896	None	None	N
L/Q	0.787	likely_pathogenic	0.8681	pathogenic	-2.25	Highly Destabilizing	0.999	D	0.866	deleterious	D	0.545926896	None	None	N
L/R	0.8385	likely_pathogenic	0.9011	pathogenic	-1.967	Destabilizing	0.997	D	0.859	deleterious	D	0.545926896	None	None	N
L/S	0.7916	likely_pathogenic	0.8943	pathogenic	-3.36	Highly Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
L/T	0.6179	likely_pathogenic	0.7665	pathogenic	-2.896	Highly Destabilizing	0.732	D	0.789	deleterious	None	None	None	None	N
L/V	0.0745	likely_benign	0.0905	benign	-1.52	Destabilizing	None	N	0.337	neutral	N	0.491951135	None	None	N
L/W	0.6358	likely_pathogenic	0.7514	pathogenic	-1.981	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
L/Y	0.6513	likely_pathogenic	0.7529	pathogenic	-1.752	Destabilizing	0.633	D	0.811	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.