TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7407	22444;22445;22446	chr2:178722680;178722679;178722678	chr2:179587407;179587406;179587405
N2AB	7090	21493;21494;21495	chr2:178722680;178722679;178722678	chr2:179587407;179587406;179587405
N2A	6163	18712;18713;18714	chr2:178722680;178722679;178722678	chr2:179587407;179587406;179587405
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-58
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.5361
• 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	rs548543520	0.213	0.001	N	0.231	0.098	0.115124310173	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
K/N	rs548543520	0.213	0.001	N	0.231	0.098	0.115124310173	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
K/N	rs548543520	0.213	0.001	N	0.231	0.098	0.115124310173	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
K/N	rs548543520	0.213	0.001	N	0.231	0.098	0.115124310173	gnomAD-4.0.0	4.05938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.87882E-04	0
K/R	None	None	0.096	N	0.481	0.101	0.181679512989	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.176	likely_benign	0.217	benign	-0.264	Destabilizing	0.055	N	0.407	neutral	None	None	None	None	N
K/C	0.5126	ambiguous	0.5899	pathogenic	-0.312	Destabilizing	0.958	D	0.563	neutral	None	None	None	None	N
K/D	0.2825	likely_benign	0.3836	ambiguous	0.064	Stabilizing	0.124	N	0.533	neutral	None	None	None	None	N
K/E	0.096	likely_benign	0.1176	benign	0.077	Stabilizing	0.042	N	0.499	neutral	N	0.424891929	None	None	N
K/F	0.5388	ambiguous	0.6435	pathogenic	-0.461	Destabilizing	0.497	N	0.59	neutral	None	None	None	None	N
K/G	0.2327	likely_benign	0.3013	benign	-0.495	Destabilizing	0.055	N	0.511	neutral	None	None	None	None	N
K/H	0.1875	likely_benign	0.2253	benign	-0.878	Destabilizing	0.497	N	0.584	neutral	None	None	None	None	N
K/I	0.2439	likely_benign	0.3075	benign	0.275	Stabilizing	0.124	N	0.581	neutral	None	None	None	None	N
K/L	0.2255	likely_benign	0.2936	benign	0.275	Stabilizing	0.001	N	0.345	neutral	None	None	None	None	N
K/M	0.1622	likely_benign	0.2022	benign	0.328	Stabilizing	0.427	N	0.575	neutral	N	0.502104706	None	None	N
K/N	0.1576	likely_benign	0.2097	benign	0.122	Stabilizing	0.001	N	0.231	neutral	N	0.440997532	None	None	N
K/P	0.5029	ambiguous	0.6367	pathogenic	0.124	Stabilizing	0.364	N	0.613	neutral	None	None	None	None	N
K/Q	0.0908	likely_benign	0.1001	benign	-0.155	Destabilizing	0.003	N	0.28	neutral	N	0.471261724	None	None	N
K/R	0.0772	likely_benign	0.0797	benign	-0.091	Destabilizing	0.096	N	0.481	neutral	N	0.449539657	None	None	N
K/S	0.1506	likely_benign	0.1884	benign	-0.499	Destabilizing	0.011	N	0.195	neutral	None	None	None	None	N
K/T	0.0899	likely_benign	0.1018	benign	-0.325	Destabilizing	0.001	N	0.255	neutral	N	0.435666283	None	None	N
K/V	0.2079	likely_benign	0.2581	benign	0.124	Stabilizing	0.004	N	0.358	neutral	None	None	None	None	N
K/W	0.5965	likely_pathogenic	0.693	pathogenic	-0.355	Destabilizing	0.958	D	0.584	neutral	None	None	None	None	N
K/Y	0.4056	ambiguous	0.513	ambiguous	-0.006	Destabilizing	0.667	D	0.585	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.