TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14217	42874;42875;42876	chr2:178633850;178633849;178633848	chr2:179498577;179498576;179498575
N2AB	12576	37951;37952;37953	chr2:178633850;178633849;178633848	chr2:179498577;179498576;179498575
N2A	11649	35170;35171;35172	chr2:178633850;178633849;178633848	chr2:179498577;179498576;179498575
N2B	5152	15679;15680;15681	chr2:178633850;178633849;178633848	chr2:179498577;179498576;179498575
Novex-1	5277	16054;16055;16056	chr2:178633850;178633849;178633848	chr2:179498577;179498576;179498575
Novex-2	5344	16255;16256;16257	chr2:178633850;178633849;178633848	chr2:179498577;179498576;179498575
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-92
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.5287
• 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
E/K	rs727503629	0.514	0.012	N	0.311	0.088	0.191931220699	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs727503629	0.514	0.012	N	0.311	0.088	0.191931220699	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs727503629	0.514	0.012	N	0.311	0.088	0.191931220699	gnomAD-4.0.0	1.85961E-06	None	None	None	None	N	None	4.00652E-05	0	None	0	0	None	0	0	0	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
E/A	0.1099	likely_benign	0.0953	benign	-0.072	Destabilizing	None	N	0.13	neutral	N	0.442353121	None	None	N
E/C	0.6252	likely_pathogenic	0.4856	ambiguous	-0.239	Destabilizing	0.676	D	0.413	neutral	None	None	None	None	N
E/D	0.0431	likely_benign	0.0401	benign	-0.352	Destabilizing	None	N	0.105	neutral	N	0.385137438	None	None	N
E/F	0.5198	ambiguous	0.4037	ambiguous	-0.025	Destabilizing	0.356	N	0.439	neutral	None	None	None	None	N
E/G	0.0588	likely_benign	0.0598	benign	-0.2	Destabilizing	None	N	0.132	neutral	N	0.292997733	None	None	N
E/H	0.2617	likely_benign	0.1856	benign	0.577	Stabilizing	0.214	N	0.365	neutral	None	None	None	None	N
E/I	0.2978	likely_benign	0.2266	benign	0.211	Stabilizing	0.214	N	0.491	neutral	None	None	None	None	N
E/K	0.1681	likely_benign	0.1421	benign	0.44	Stabilizing	0.012	N	0.311	neutral	N	0.432008689	None	None	N
E/L	0.2945	likely_benign	0.2384	benign	0.211	Stabilizing	0.072	N	0.447	neutral	None	None	None	None	N
E/M	0.3633	ambiguous	0.2946	benign	-0.011	Destabilizing	0.628	D	0.416	neutral	None	None	None	None	N
E/N	0.0732	likely_benign	0.0479	benign	0.054	Stabilizing	None	N	0.105	neutral	None	None	None	None	N
E/P	0.4428	ambiguous	0.3895	ambiguous	0.135	Stabilizing	0.136	N	0.419	neutral	None	None	None	None	N
E/Q	0.1351	likely_benign	0.1195	benign	0.088	Stabilizing	0.055	N	0.362	neutral	N	0.485490454	None	None	N
E/R	0.254	likely_benign	0.2095	benign	0.69	Stabilizing	0.072	N	0.322	neutral	None	None	None	None	N
E/S	0.0917	likely_benign	0.0745	benign	-0.048	Destabilizing	0.007	N	0.269	neutral	None	None	None	None	N
E/T	0.1308	likely_benign	0.1108	benign	0.071	Stabilizing	0.016	N	0.328	neutral	None	None	None	None	N
E/V	0.1994	likely_benign	0.1554	benign	0.135	Stabilizing	0.029	N	0.397	neutral	N	0.4962029	None	None	N
E/W	0.7413	likely_pathogenic	0.6576	pathogenic	0.052	Stabilizing	0.864	D	0.428	neutral	None	None	None	None	N
E/Y	0.3011	likely_benign	0.2151	benign	0.202	Stabilizing	0.628	D	0.429	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.