TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32053	96382;96383;96384	chr2:178543987;178543986;178543985	chr2:179408714;179408713;179408712
N2AB	30412	91459;91460;91461	chr2:178543987;178543986;178543985	chr2:179408714;179408713;179408712
N2A	29485	88678;88679;88680	chr2:178543987;178543986;178543985	chr2:179408714;179408713;179408712
N2B	22988	69187;69188;69189	chr2:178543987;178543986;178543985	chr2:179408714;179408713;179408712
Novex-1	23113	69562;69563;69564	chr2:178543987;178543986;178543985	chr2:179408714;179408713;179408712
Novex-2	23180	69763;69764;69765	chr2:178543987;178543986;178543985	chr2:179408714;179408713;179408712
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-153
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.5887
• 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	rs906167122	None	0.939	N	0.341	0.175	0.634385825132	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	rs906167122	None	0.939	N	0.341	0.175	0.634385825132	gnomAD-4.0.0	4.95805E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78133E-06	0	0
I/T	rs62621236	-0.092	0.028	N	0.239	0.224	None	gnomAD-2.1.1	8.3463E-02	None	None	None	None	N	None	1.45303E-01	2.02449E-01	None	2.97642E-02	2.7607E-02	None	1.82876E-01	None	5.70709E-02	3.42392E-02	6.49369E-02
I/T	rs62621236	-0.092	0.028	N	0.239	0.224	None	gnomAD-3.1.2	8.3273E-02	None	None	None	None	N	None	1.44115E-01	1.65224E-01	4.93421E-02	2.9683E-02	2.49227E-02	None	5.83632E-02	8.22785E-02	3.30608E-02	1.78068E-01	7.12237E-02
I/T	rs62621236	-0.092	0.028	N	0.239	0.224	None	1000 genomes	1.15815E-01	None	None	None	None	N	None	1.46E-01	1.643E-01	None	None	2.58E-02	5.17E-02	None	None	None	1.994E-01	None
I/T	rs62621236	-0.092	0.028	N	0.239	0.224	None	gnomAD-4.0.0	5.45041E-02	None	None	None	None	N	None	1.47681E-01	1.91307E-01	None	2.93621E-02	1.50914E-02	None	5.90874E-02	5.49868E-02	3.39113E-02	1.7511E-01	5.99808E-02
I/V	None	None	0.001	N	0.169	0.08	0.355658859761	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	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	0.1381	likely_benign	0.1512	benign	-1.115	Destabilizing	0.373	N	0.318	neutral	None	None	None	None	N
I/C	0.4378	ambiguous	0.4795	ambiguous	-0.732	Destabilizing	0.996	D	0.343	neutral	None	None	None	None	N
I/D	0.4299	ambiguous	0.4537	ambiguous	-0.482	Destabilizing	0.953	D	0.415	neutral	None	None	None	None	N
I/E	0.3359	likely_benign	0.3539	ambiguous	-0.522	Destabilizing	0.953	D	0.391	neutral	None	None	None	None	N
I/F	0.1223	likely_benign	0.1301	benign	-0.845	Destabilizing	0.884	D	0.304	neutral	N	0.486863108	None	None	N
I/G	0.3157	likely_benign	0.3589	ambiguous	-1.374	Destabilizing	0.854	D	0.413	neutral	None	None	None	None	N
I/H	0.3199	likely_benign	0.3525	ambiguous	-0.64	Destabilizing	0.996	D	0.418	neutral	None	None	None	None	N
I/K	0.2351	likely_benign	0.2488	benign	-0.755	Destabilizing	0.953	D	0.395	neutral	None	None	None	None	N
I/L	0.0978	likely_benign	0.1014	benign	-0.516	Destabilizing	0.164	N	0.225	neutral	N	0.453750612	None	None	N
I/M	0.0739	likely_benign	0.0769	benign	-0.464	Destabilizing	0.939	D	0.341	neutral	N	0.47689683	None	None	N
I/N	0.1437	likely_benign	0.156	benign	-0.53	Destabilizing	0.939	D	0.424	neutral	N	0.473875168	None	None	N
I/P	0.62	likely_pathogenic	0.6182	pathogenic	-0.683	Destabilizing	0.984	D	0.419	neutral	None	None	None	None	N
I/Q	0.2511	likely_benign	0.2753	benign	-0.704	Destabilizing	0.984	D	0.416	neutral	None	None	None	None	N
I/R	0.1959	likely_benign	0.2047	benign	-0.204	Destabilizing	0.953	D	0.42	neutral	None	None	None	None	N
I/S	0.1331	likely_benign	0.1433	benign	-1.066	Destabilizing	0.521	D	0.367	neutral	N	0.426041148	None	None	N
I/T	0.0811	likely_benign	0.0898	benign	-0.988	Destabilizing	0.028	N	0.239	neutral	N	0.412653351	None	None	N
I/V	0.0613	likely_benign	0.0649	benign	-0.683	Destabilizing	0.001	N	0.169	neutral	N	0.388123052	None	None	N
I/W	0.6478	likely_pathogenic	0.6488	pathogenic	-0.899	Destabilizing	0.996	D	0.465	neutral	None	None	None	None	N
I/Y	0.3939	ambiguous	0.4054	ambiguous	-0.664	Destabilizing	0.953	D	0.332	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.