TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20647	62164;62165;62166	chr2:178589786;178589785;178589784	chr2:179454513;179454512;179454511
N2AB	19006	57241;57242;57243	chr2:178589786;178589785;178589784	chr2:179454513;179454512;179454511
N2A	18079	54460;54461;54462	chr2:178589786;178589785;178589784	chr2:179454513;179454512;179454511
N2B	11582	34969;34970;34971	chr2:178589786;178589785;178589784	chr2:179454513;179454512;179454511
Novex-1	11707	35344;35345;35346	chr2:178589786;178589785;178589784	chr2:179454513;179454512;179454511
Novex-2	11774	35545;35546;35547	chr2:178589786;178589785;178589784	chr2:179454513;179454512;179454511
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-37
• Domain position: 79
• Structural Position: 113
• Q(SASA): 0.8895
• Predicted PPI site: I

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/Q	rs751883286	0.303	1.0	N	0.665	0.399	0.402755899245	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
K/Q	rs751883286	0.303	1.0	N	0.665	0.399	0.402755899245	gnomAD-4.0.0	1.59175E-06	None	None	None	None	I	None	0	2.28697E-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
K/A	0.7307	likely_pathogenic	0.7476	pathogenic	-0.052	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	I
K/C	0.9352	likely_pathogenic	0.9425	pathogenic	-0.236	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
K/D	0.8838	likely_pathogenic	0.8854	pathogenic	0.107	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
K/E	0.5491	ambiguous	0.5955	pathogenic	0.102	Stabilizing	0.999	D	0.595	neutral	N	0.477325613	None	None	I
K/F	0.9721	likely_pathogenic	0.9733	pathogenic	-0.337	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
K/G	0.8646	likely_pathogenic	0.8776	pathogenic	-0.235	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	I
K/H	0.668	likely_pathogenic	0.6953	pathogenic	-0.55	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	I
K/I	0.6873	likely_pathogenic	0.689	pathogenic	0.345	Stabilizing	1.0	D	0.64	neutral	N	0.509862105	None	None	I
K/L	0.7622	likely_pathogenic	0.7648	pathogenic	0.345	Stabilizing	1.0	D	0.553	neutral	None	None	None	None	I
K/M	0.6217	likely_pathogenic	0.6399	pathogenic	0.253	Stabilizing	1.0	D	0.606	neutral	None	None	None	None	I
K/N	0.8421	likely_pathogenic	0.8481	pathogenic	0.23	Stabilizing	1.0	D	0.67	neutral	N	0.474318072	None	None	I
K/P	0.9073	likely_pathogenic	0.8826	pathogenic	0.24	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/Q	0.3736	ambiguous	0.4127	ambiguous	0.014	Stabilizing	1.0	D	0.665	neutral	N	0.514035774	None	None	I
K/R	0.1275	likely_benign	0.1414	benign	-0.007	Destabilizing	0.999	D	0.516	neutral	N	0.509899391	None	None	I
K/S	0.8128	likely_pathogenic	0.8286	pathogenic	-0.291	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
K/T	0.4992	ambiguous	0.5175	ambiguous	-0.15	Destabilizing	1.0	D	0.612	neutral	N	0.468784664	None	None	I
K/V	0.6448	likely_pathogenic	0.6457	pathogenic	0.24	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	I
K/W	0.9657	likely_pathogenic	0.9709	pathogenic	-0.327	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
K/Y	0.9245	likely_pathogenic	0.9304	pathogenic	0.038	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	I

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.