TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1001	3226;3227;3228	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630
N2AB	1001	3226;3227;3228	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630
N2A	1001	3226;3227;3228	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630
N2B	955	3088;3089;3090	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630
Novex-1	955	3088;3089;3090	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630
Novex-2	955	3088;3089;3090	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630
Novex-3	1001	3226;3227;3228	chr2:178782905;178782904;178782903	chr2:179647632;179647631;179647630

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-3
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.263
• 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
M/I	rs794729522	None	None	N	0.168	0.143	0.292787519742	gnomAD-4.0.0	6.36231E-06	None	None	None	None	N	None	0	0	None	9.53107E-05	5.54785E-05	None	0	0	0	0	0
M/R	rs148269839	-0.568	0.065	N	0.523	0.378	None	gnomAD-2.1.1	1.13354E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	3.98E-05	2.25334E-04	2.77393E-04
M/R	rs148269839	-0.568	0.065	N	0.523	0.378	None	gnomAD-3.1.2	1.18247E-04	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.64535E-04	0	0
M/R	rs148269839	-0.568	0.065	N	0.523	0.378	None	gnomAD-4.0.0	1.44358E-04	None	None	None	None	N	None	0	1.66644E-05	None	0	0	None	0	0	1.93218E-04	0	6.40184E-05
M/T	rs148269839	-1.37	None	N	0.219	0.348	0.677378689129	gnomAD-2.1.1	8.86E-05	None	None	None	None	N	None	0	1.69338E-04	None	0	0	None	0	None	6.76698E-04	7.77E-06	1.38696E-04
M/T	rs148269839	-1.37	None	N	0.219	0.348	0.677378689129	gnomAD-3.1.2	5.91E-05	None	None	None	None	N	None	0	1.30839E-04	0	0	0	None	4.70544E-04	0	1.47E-05	0	4.78011E-04
M/T	rs148269839	-1.37	None	N	0.219	0.348	0.677378689129	gnomAD-4.0.0	3.71737E-05	None	None	None	None	N	None	0	1.4998E-04	None	0	0	None	6.40205E-04	0	7.62702E-06	0	1.60046E-05
M/V	None	None	None	N	0.162	0.103	0.148003135375	gnomAD-4.0.0	1.20032E-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
M/A	0.6373	likely_pathogenic	0.6193	pathogenic	-1.59	Destabilizing	0.004	N	0.309	neutral	None	None	None	None	N
M/C	0.8942	likely_pathogenic	0.8951	pathogenic	-1.699	Destabilizing	0.497	N	0.468	neutral	None	None	None	None	N
M/D	0.94	likely_pathogenic	0.9311	pathogenic	-0.707	Destabilizing	0.085	N	0.528	neutral	None	None	None	None	N
M/E	0.6473	likely_pathogenic	0.6283	pathogenic	-0.623	Destabilizing	0.085	N	0.495	neutral	None	None	None	None	N
M/F	0.6156	likely_pathogenic	0.5918	pathogenic	-0.442	Destabilizing	0.022	N	0.415	neutral	None	None	None	None	N
M/G	0.8791	likely_pathogenic	0.8673	pathogenic	-1.96	Destabilizing	0.037	N	0.477	neutral	None	None	None	None	N
M/H	0.6369	likely_pathogenic	0.6201	pathogenic	-1.203	Destabilizing	0.497	N	0.502	neutral	None	None	None	None	N
M/I	0.5021	ambiguous	0.4648	ambiguous	-0.611	Destabilizing	None	N	0.168	neutral	N	0.346134392	None	None	N
M/K	0.315	likely_benign	0.3119	benign	-0.603	Destabilizing	0.028	N	0.469	neutral	N	0.407202419	None	None	N
M/L	0.1542	likely_benign	0.149	benign	-0.611	Destabilizing	None	N	0.173	neutral	N	0.334550611	None	None	N
M/N	0.6918	likely_pathogenic	0.6537	pathogenic	-0.596	Destabilizing	0.085	N	0.54	neutral	None	None	None	None	N
M/P	0.9973	likely_pathogenic	0.9971	pathogenic	-0.91	Destabilizing	0.22	N	0.539	neutral	None	None	None	None	N
M/Q	0.3162	likely_benign	0.3044	benign	-0.577	Destabilizing	0.22	N	0.435	neutral	None	None	None	None	N
M/R	0.3789	ambiguous	0.3789	ambiguous	-0.35	Destabilizing	0.065	N	0.523	neutral	N	0.389882439	None	None	N
M/S	0.6317	likely_pathogenic	0.5963	pathogenic	-1.251	Destabilizing	0.009	N	0.405	neutral	None	None	None	None	N
M/T	0.3053	likely_benign	0.2823	benign	-1.046	Destabilizing	None	N	0.219	neutral	N	0.32480407	None	None	N
M/V	0.1274	likely_benign	0.1172	benign	-0.91	Destabilizing	None	N	0.162	neutral	N	0.338115172	None	None	N
M/W	0.8418	likely_pathogenic	0.8434	pathogenic	-0.492	Destabilizing	0.788	D	0.465	neutral	None	None	None	None	N
M/Y	0.8252	likely_pathogenic	0.8139	pathogenic	-0.449	Destabilizing	0.085	N	0.523	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.