TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6075	18448;18449;18450	chr2:178730177;178730176;178730175	chr2:179594904;179594903;179594902
N2AB	5758	17497;17498;17499	chr2:178730177;178730176;178730175	chr2:179594904;179594903;179594902
N2A	4831	14716;14717;14718	chr2:178730177;178730176;178730175	chr2:179594904;179594903;179594902
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-44
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2937
• 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/T	None	None	0.997	N	0.665	0.389	0.510230903827	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	0.326	likely_benign	0.3243	benign	-0.054	Destabilizing	0.983	D	0.532	neutral	None	None	None	None	N
K/C	0.7811	likely_pathogenic	0.7873	pathogenic	-0.034	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/D	0.5069	ambiguous	0.5606	ambiguous	0.13	Stabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
K/E	0.1628	likely_benign	0.1777	benign	0.15	Stabilizing	0.977	D	0.481	neutral	N	0.514817713	None	None	N
K/F	0.7752	likely_pathogenic	0.7908	pathogenic	-0.177	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/G	0.3769	ambiguous	0.3813	ambiguous	-0.302	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
K/H	0.3365	likely_benign	0.3558	ambiguous	-0.696	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
K/I	0.4561	ambiguous	0.4747	ambiguous	0.532	Stabilizing	0.997	D	0.776	deleterious	N	0.499041006	None	None	N
K/L	0.4079	ambiguous	0.4217	ambiguous	0.532	Stabilizing	0.995	D	0.641	neutral	None	None	None	None	N
K/M	0.2895	likely_benign	0.3013	benign	0.484	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/N	0.3553	ambiguous	0.4012	ambiguous	0.296	Stabilizing	0.993	D	0.682	prob.neutral	N	0.4854922	None	None	N
K/P	0.842	likely_pathogenic	0.8416	pathogenic	0.366	Stabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
K/Q	0.1363	likely_benign	0.142	benign	0.091	Stabilizing	0.993	D	0.665	neutral	N	0.479051701	None	None	N
K/R	0.088	likely_benign	0.0877	benign	-0.048	Destabilizing	0.235	N	0.295	neutral	N	0.498312252	None	None	N
K/S	0.3429	ambiguous	0.3648	ambiguous	-0.256	Destabilizing	0.983	D	0.595	neutral	None	None	None	None	N
K/T	0.1691	likely_benign	0.1749	benign	-0.072	Destabilizing	0.997	D	0.665	neutral	N	0.49034613	None	None	N
K/V	0.3733	ambiguous	0.3767	ambiguous	0.366	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
K/W	0.8084	likely_pathogenic	0.8161	pathogenic	-0.139	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/Y	0.6828	likely_pathogenic	0.7099	pathogenic	0.21	Stabilizing	0.999	D	0.749	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.