TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29150	87673;87674;87675	chr2:178557906;178557905;178557904	chr2:179422633;179422632;179422631
N2AB	27509	82750;82751;82752	chr2:178557906;178557905;178557904	chr2:179422633;179422632;179422631
N2A	26582	79969;79970;79971	chr2:178557906;178557905;178557904	chr2:179422633;179422632;179422631
N2B	20085	60478;60479;60480	chr2:178557906;178557905;178557904	chr2:179422633;179422632;179422631
Novex-1	20210	60853;60854;60855	chr2:178557906;178557905;178557904	chr2:179422633;179422632;179422631
Novex-2	20277	61054;61055;61056	chr2:178557906;178557905;178557904	chr2:179422633;179422632;179422631
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: Fn3-100
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.3238
• 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
I/K	None	None	0.879	N	0.591	0.393	0.77209592603	gnomAD-4.0.0	6.84336E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99426E-07	0	0
I/L	rs189030321	-0.823	0.084	N	0.199	0.075	0.227260227426	gnomAD-2.1.1	3.57E-05	None	None	None	None	I	None	0	1.13148E-04	None	0	0	None	0	None	0	3.12E-05	2.80899E-04
I/L	rs189030321	-0.823	0.084	N	0.199	0.075	0.227260227426	gnomAD-3.1.2	2.49652E-04	None	None	None	None	I	None	2.41E-05	1.8984E-03	0	0	0	None	0	0	7.35E-05	0	1.43267E-03
I/L	rs189030321	-0.823	0.084	N	0.199	0.075	0.227260227426	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	2.9E-03	None	None	0	0	None	None	None	0	None
I/L	rs189030321	-0.823	0.084	N	0.199	0.075	0.227260227426	gnomAD-4.0.0	4.52409E-05	None	None	None	None	I	None	2.66446E-05	6.99767E-04	None	0	0	None	0	3.30033E-04	1.7799E-05	1.09786E-05	8.0023E-05
I/T	rs373106927	-1.3	0.505	N	0.421	0.334	None	gnomAD-2.1.1	8.57E-05	None	None	None	None	I	None	0	1.97997E-04	None	1.06321E-03	5.12E-05	None	0	None	0	3.12E-05	1.40449E-04
I/T	rs373106927	-1.3	0.505	N	0.421	0.334	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	0	0	0	1.72811E-03	0	None	0	0	1.47E-05	0	0
I/T	rs373106927	-1.3	0.505	N	0.421	0.334	None	gnomAD-4.0.0	3.96659E-05	None	None	None	None	I	None	0	1.33329E-04	None	1.3173E-03	0	None	0	0	8.47558E-06	1.09782E-05	9.60584E-05
I/V	rs189030321	-1.047	None	N	0.098	0.083	0.171388866994	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs189030321	-1.047	None	N	0.098	0.083	0.171388866994	gnomAD-4.0.0	6.84344E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15934E-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
I/A	0.3695	ambiguous	0.3652	ambiguous	-1.631	Destabilizing	0.218	N	0.433	neutral	None	None	None	None	I
I/C	0.6127	likely_pathogenic	0.6179	pathogenic	-1.399	Destabilizing	0.973	D	0.481	neutral	None	None	None	None	I
I/D	0.7762	likely_pathogenic	0.7881	pathogenic	-1.041	Destabilizing	0.906	D	0.609	neutral	None	None	None	None	I
I/E	0.6503	likely_pathogenic	0.633	pathogenic	-1.031	Destabilizing	0.906	D	0.586	neutral	None	None	None	None	I
I/F	0.2372	likely_benign	0.2642	benign	-1.312	Destabilizing	0.826	D	0.469	neutral	None	None	None	None	I
I/G	0.6972	likely_pathogenic	0.7261	pathogenic	-1.944	Destabilizing	0.906	D	0.542	neutral	None	None	None	None	I
I/H	0.6569	likely_pathogenic	0.6598	pathogenic	-1.259	Destabilizing	0.991	D	0.605	neutral	None	None	None	None	I
I/K	0.468	ambiguous	0.4482	ambiguous	-0.997	Destabilizing	0.879	D	0.591	neutral	N	0.486563958	None	None	I
I/L	0.1574	likely_benign	0.1741	benign	-0.845	Destabilizing	0.084	N	0.199	neutral	N	0.463071023	None	None	I
I/M	0.1281	likely_benign	0.1352	benign	-0.811	Destabilizing	0.782	D	0.521	neutral	D	0.52533299	None	None	I
I/N	0.408	ambiguous	0.3932	ambiguous	-0.863	Destabilizing	0.967	D	0.601	neutral	None	None	None	None	I
I/P	0.803	likely_pathogenic	0.8187	pathogenic	-1.077	Destabilizing	0.967	D	0.605	neutral	None	None	None	None	I
I/Q	0.5407	ambiguous	0.5278	ambiguous	-1.052	Destabilizing	0.967	D	0.608	neutral	None	None	None	None	I
I/R	0.407	ambiguous	0.3915	ambiguous	-0.522	Destabilizing	0.879	D	0.602	neutral	N	0.495010083	None	None	I
I/S	0.3874	ambiguous	0.3734	ambiguous	-1.546	Destabilizing	0.826	D	0.503	neutral	None	None	None	None	I
I/T	0.2067	likely_benign	0.1902	benign	-1.414	Destabilizing	0.505	D	0.421	neutral	N	0.476885682	None	None	I
I/V	0.0547	likely_benign	0.0566	benign	-1.077	Destabilizing	None	N	0.098	neutral	N	0.356228773	None	None	I
I/W	0.8824	likely_pathogenic	0.8918	pathogenic	-1.344	Destabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	I
I/Y	0.6277	likely_pathogenic	0.6469	pathogenic	-1.076	Destabilizing	0.906	D	0.517	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.