TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6953	21082;21083;21084	chr2:178724518;178724517;178724516	chr2:179589245;179589244;179589243
N2AB	6636	20131;20132;20133	chr2:178724518;178724517;178724516	chr2:179589245;179589244;179589243
N2A	5709	17350;17351;17352	chr2:178724518;178724517;178724516	chr2:179589245;179589244;179589243
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-54
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5891
• 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/E	None	None	0.219	N	0.143	0.173	0.338592109245	gnomAD-4.0.0	4.15281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.54147E-06	0	1.67915E-05

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	0.2918	likely_benign	0.3253	benign	-0.077	Destabilizing	0.985	D	0.537	neutral	None	None	None	None	N
K/C	0.8171	likely_pathogenic	0.841	pathogenic	-0.204	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/D	0.4819	ambiguous	0.5153	ambiguous	0.184	Stabilizing	0.971	D	0.521	neutral	None	None	None	None	N
K/E	0.1147	likely_benign	0.1343	benign	0.204	Stabilizing	0.219	N	0.143	neutral	N	0.501563201	None	None	N
K/F	0.8046	likely_pathogenic	0.8337	pathogenic	-0.217	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
K/G	0.4238	ambiguous	0.4595	ambiguous	-0.307	Destabilizing	0.993	D	0.519	neutral	None	None	None	None	N
K/H	0.3974	ambiguous	0.4324	ambiguous	-0.649	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
K/I	0.4183	ambiguous	0.4576	ambiguous	0.455	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	N
K/L	0.4006	ambiguous	0.4533	ambiguous	0.455	Stabilizing	0.993	D	0.493	neutral	None	None	None	None	N
K/M	0.191	likely_benign	0.2235	benign	0.287	Stabilizing	1.0	D	0.549	neutral	N	0.510068143	None	None	N
K/N	0.33	likely_benign	0.3711	ambiguous	0.225	Stabilizing	0.99	D	0.475	neutral	N	0.521997188	None	None	N
K/P	0.4884	ambiguous	0.4833	ambiguous	0.307	Stabilizing	0.999	D	0.481	neutral	None	None	None	None	N
K/Q	0.1272	likely_benign	0.1412	benign	0.046	Stabilizing	0.98	D	0.528	neutral	N	0.490692847	None	None	N
K/R	0.1078	likely_benign	0.1088	benign	-0.078	Destabilizing	0.98	D	0.477	neutral	N	0.502083276	None	None	N
K/S	0.3584	ambiguous	0.4079	ambiguous	-0.321	Destabilizing	0.985	D	0.501	neutral	None	None	None	None	N
K/T	0.1459	likely_benign	0.1677	benign	-0.14	Destabilizing	0.99	D	0.501	neutral	N	0.515551219	None	None	N
K/V	0.3737	ambiguous	0.4062	ambiguous	0.307	Stabilizing	0.998	D	0.474	neutral	None	None	None	None	N
K/W	0.8394	likely_pathogenic	0.8535	pathogenic	-0.185	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
K/Y	0.6485	likely_pathogenic	0.6794	pathogenic	0.164	Stabilizing	0.999	D	0.61	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.