TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17815	53668;53669;53670	chr2:178607159;178607158;178607157	chr2:179471886;179471885;179471884
N2AB	16174	48745;48746;48747	chr2:178607159;178607158;178607157	chr2:179471886;179471885;179471884
N2A	15247	45964;45965;45966	chr2:178607159;178607158;178607157	chr2:179471886;179471885;179471884
N2B	8750	26473;26474;26475	chr2:178607159;178607158;178607157	chr2:179471886;179471885;179471884
Novex-1	8875	26848;26849;26850	chr2:178607159;178607158;178607157	chr2:179471886;179471885;179471884
Novex-2	8942	27049;27050;27051	chr2:178607159;178607158;178607157	chr2:179471886;179471885;179471884
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-17
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.153
• 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
I/M	rs370843257	-0.74	0.966	N	0.541	0.204	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	2.67E-05	1.65893E-04
I/M	rs370843257	-0.74	0.966	N	0.541	0.204	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs370843257	-0.74	0.966	N	0.541	0.204	None	gnomAD-4.0.0	3.71992E-06	None	None	None	None	N	None	0	1.66795E-05	None	0	0	None	0	0	2.54386E-06	0	3.20431E-05
I/T	rs374563054	-1.764	0.801	N	0.465	0.318	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	2.48242E-04	0	None	0	0	None	0	None	0	0	0
I/T	rs374563054	-1.764	0.801	N	0.465	0.318	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.93153E-04	0	0	0	0	None	0	0	0	0	0
I/T	rs374563054	-1.764	0.801	N	0.465	0.318	None	gnomAD-4.0.0	1.61189E-05	None	None	None	None	N	None	2.93529E-04	1.66728E-05	None	0	0	None	0	0	2.54392E-06	0	0
I/V	rs368065637	-1.128	0.005	N	0.147	0.086	None	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	3.27E-05	None	0	3.56E-05	0
I/V	rs368065637	-1.128	0.005	N	0.147	0.086	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs368065637	-1.128	0.005	N	0.147	0.086	None	gnomAD-4.0.0	3.71993E-05	None	None	None	None	N	None	5.34359E-05	0	None	0	0	None	0	1.6469E-04	4.15504E-05	3.29468E-05	4.80677E-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
I/A	0.4585	ambiguous	0.518	ambiguous	-1.593	Destabilizing	0.525	D	0.478	neutral	None	None	None	None	N
I/C	0.8587	likely_pathogenic	0.894	pathogenic	-0.863	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
I/D	0.9486	likely_pathogenic	0.9587	pathogenic	-1.2	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	N
I/E	0.8322	likely_pathogenic	0.8494	pathogenic	-1.184	Destabilizing	0.974	D	0.595	neutral	None	None	None	None	N
I/F	0.379	ambiguous	0.3876	ambiguous	-1.058	Destabilizing	0.016	N	0.33	neutral	None	None	None	None	N
I/G	0.877	likely_pathogenic	0.8999	pathogenic	-1.928	Destabilizing	0.974	D	0.589	neutral	None	None	None	None	N
I/H	0.8768	likely_pathogenic	0.8869	pathogenic	-1.213	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
I/K	0.7784	likely_pathogenic	0.7899	pathogenic	-1.222	Destabilizing	0.966	D	0.598	neutral	N	0.464743104	None	None	N
I/L	0.1566	likely_benign	0.1709	benign	-0.74	Destabilizing	0.267	N	0.339	neutral	N	0.40802303	None	None	N
I/M	0.1356	likely_benign	0.1431	benign	-0.521	Destabilizing	0.966	D	0.541	neutral	N	0.440636881	None	None	N
I/N	0.7315	likely_pathogenic	0.7499	pathogenic	-1.053	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
I/P	0.9661	likely_pathogenic	0.9712	pathogenic	-0.993	Destabilizing	0.991	D	0.618	neutral	None	None	None	None	N
I/Q	0.7385	likely_pathogenic	0.7499	pathogenic	-1.197	Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
I/R	0.7223	likely_pathogenic	0.7297	pathogenic	-0.64	Destabilizing	0.966	D	0.623	neutral	N	0.473727947	None	None	N
I/S	0.5993	likely_pathogenic	0.6274	pathogenic	-1.614	Destabilizing	0.915	D	0.557	neutral	None	None	None	None	N
I/T	0.324	likely_benign	0.3677	ambiguous	-1.485	Destabilizing	0.801	D	0.465	neutral	N	0.410583333	None	None	N
I/V	0.0837	likely_benign	0.0912	benign	-0.993	Destabilizing	0.005	N	0.147	neutral	N	0.417354589	None	None	N
I/W	0.9168	likely_pathogenic	0.9211	pathogenic	-1.197	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
I/Y	0.8116	likely_pathogenic	0.8097	pathogenic	-0.966	Destabilizing	0.904	D	0.519	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.