TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14645	44158;44159;44160	chr2:178631115;178631114;178631113	chr2:179495842;179495841;179495840
N2AB	13004	39235;39236;39237	chr2:178631115;178631114;178631113	chr2:179495842;179495841;179495840
N2A	12077	36454;36455;36456	chr2:178631115;178631114;178631113	chr2:179495842;179495841;179495840
N2B	5580	16963;16964;16965	chr2:178631115;178631114;178631113	chr2:179495842;179495841;179495840
Novex-1	5705	17338;17339;17340	chr2:178631115;178631114;178631113	chr2:179495842;179495841;179495840
Novex-2	5772	17539;17540;17541	chr2:178631115;178631114;178631113	chr2:179495842;179495841;179495840
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-97
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.5402
• 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
K/N	None	None	0.999	N	0.62	0.291	0.361958692863	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
K/A	0.6769	likely_pathogenic	0.7236	pathogenic	-0.599	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	N
K/C	0.8823	likely_pathogenic	0.8891	pathogenic	-0.704	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
K/D	0.8225	likely_pathogenic	0.8709	pathogenic	0.041	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/E	0.2784	likely_benign	0.3517	ambiguous	0.124	Stabilizing	0.996	D	0.498	neutral	N	0.50574142	None	None	N
K/F	0.9132	likely_pathogenic	0.9199	pathogenic	-0.47	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/G	0.66	likely_pathogenic	0.7142	pathogenic	-0.922	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
K/H	0.4358	ambiguous	0.4607	ambiguous	-1.225	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/I	0.6809	likely_pathogenic	0.6996	pathogenic	0.219	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/L	0.5772	likely_pathogenic	0.6007	pathogenic	0.219	Stabilizing	1.0	D	0.606	neutral	None	None	None	None	N
K/M	0.4834	ambiguous	0.5176	ambiguous	0.166	Stabilizing	1.0	D	0.641	neutral	D	0.553055496	None	None	N
K/N	0.6189	likely_pathogenic	0.6834	pathogenic	-0.358	Destabilizing	0.999	D	0.62	neutral	N	0.512342518	None	None	N
K/P	0.7869	likely_pathogenic	0.8418	pathogenic	-0.023	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/Q	0.1786	likely_benign	0.1905	benign	-0.519	Destabilizing	0.999	D	0.605	neutral	N	0.506745355	None	None	N
K/R	0.0899	likely_benign	0.0893	benign	-0.464	Destabilizing	0.884	D	0.246	neutral	N	0.50027385	None	None	N
K/S	0.6708	likely_pathogenic	0.7188	pathogenic	-1.094	Destabilizing	0.998	D	0.552	neutral	None	None	None	None	N
K/T	0.3982	ambiguous	0.4389	ambiguous	-0.813	Destabilizing	0.999	D	0.675	prob.neutral	N	0.510923128	None	None	N
K/V	0.6612	likely_pathogenic	0.681	pathogenic	-0.023	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
K/W	0.8598	likely_pathogenic	0.8673	pathogenic	-0.298	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
K/Y	0.8066	likely_pathogenic	0.823	pathogenic	0.008	Stabilizing	1.0	D	0.665	neutral	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.