TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15922	47989;47990;47991	chr2:178617231;178617230;178617229	chr2:179481958;179481957;179481956
N2AB	14281	43066;43067;43068	chr2:178617231;178617230;178617229	chr2:179481958;179481957;179481956
N2A	13354	40285;40286;40287	chr2:178617231;178617230;178617229	chr2:179481958;179481957;179481956
N2B	6857	20794;20795;20796	chr2:178617231;178617230;178617229	chr2:179481958;179481957;179481956
Novex-1	6982	21169;21170;21171	chr2:178617231;178617230;178617229	chr2:179481958;179481957;179481956
Novex-2	7049	21370;21371;21372	chr2:178617231;178617230;178617229	chr2:179481958;179481957;179481956
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-3
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.1773
• 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
T/A	rs2057504712	None	0.201	N	0.263	0.169	0.225902525712	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/I	rs2057504360	None	0.379	N	0.369	0.385	0.38225645794	gnomAD-4.0.0	2.1552E-06	None	None	None	None	N	None	0	0	None	0	8.23497E-05	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
T/A	0.1096	likely_benign	0.1181	benign	-0.494	Destabilizing	0.201	N	0.263	neutral	N	0.478272049	None	None	N
T/C	0.4596	ambiguous	0.4801	ambiguous	-0.37	Destabilizing	0.992	D	0.429	neutral	None	None	None	None	N
T/D	0.3815	ambiguous	0.3999	ambiguous	0.32	Stabilizing	0.617	D	0.417	neutral	None	None	None	None	N
T/E	0.3032	likely_benign	0.3144	benign	0.261	Stabilizing	0.617	D	0.363	neutral	None	None	None	None	N
T/F	0.3133	likely_benign	0.3347	benign	-0.922	Destabilizing	0.92	D	0.488	neutral	None	None	None	None	N
T/G	0.2849	likely_benign	0.3233	benign	-0.645	Destabilizing	0.617	D	0.381	neutral	None	None	None	None	N
T/H	0.3037	likely_benign	0.3093	benign	-0.879	Destabilizing	0.992	D	0.471	neutral	None	None	None	None	N
T/I	0.2368	likely_benign	0.2465	benign	-0.211	Destabilizing	0.379	N	0.369	neutral	N	0.516983981	None	None	N
T/K	0.2011	likely_benign	0.1933	benign	-0.368	Destabilizing	0.617	D	0.369	neutral	None	None	None	None	N
T/L	0.1393	likely_benign	0.1474	benign	-0.211	Destabilizing	0.25	N	0.35	neutral	None	None	None	None	N
T/M	0.1218	likely_benign	0.1335	benign	-0.066	Destabilizing	0.92	D	0.443	neutral	None	None	None	None	N
T/N	0.1464	likely_benign	0.1589	benign	-0.204	Destabilizing	0.549	D	0.339	neutral	N	0.48052044	None	None	N
T/P	0.1491	likely_benign	0.1638	benign	-0.276	Destabilizing	0.004	N	0.313	neutral	N	0.484446874	None	None	N
T/Q	0.2555	likely_benign	0.2651	benign	-0.403	Destabilizing	0.92	D	0.449	neutral	None	None	None	None	N
T/R	0.1944	likely_benign	0.1765	benign	-0.105	Destabilizing	0.92	D	0.449	neutral	None	None	None	None	N
T/S	0.1252	likely_benign	0.139	benign	-0.474	Destabilizing	0.02	N	0.135	neutral	N	0.436024465	None	None	N
T/V	0.1774	likely_benign	0.1881	benign	-0.276	Destabilizing	0.021	N	0.172	neutral	None	None	None	None	N
T/W	0.6219	likely_pathogenic	0.6205	pathogenic	-0.892	Destabilizing	0.992	D	0.553	neutral	None	None	None	None	N
T/Y	0.3404	ambiguous	0.3589	ambiguous	-0.616	Destabilizing	0.972	D	0.485	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.