TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9121	27586;27587;27588	chr2:178712561;178712560;178712559	chr2:179577288;179577287;179577286
N2AB	8804	26635;26636;26637	chr2:178712561;178712560;178712559	chr2:179577288;179577287;179577286
N2A	7877	23854;23855;23856	chr2:178712561;178712560;178712559	chr2:179577288;179577287;179577286
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-77
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.5272
• 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
Y/C	rs774681899	0.118	0.975	N	0.222	0.344	0.589725459201	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
Y/C	rs774681899	0.118	0.975	N	0.222	0.344	0.589725459201	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs774681899	0.118	0.975	N	0.222	0.344	0.589725459201	gnomAD-4.0.0	1.30186E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.61084E-05	0	3.20451E-05

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
Y/A	0.2242	likely_benign	0.2515	benign	-1.884	Destabilizing	0.495	N	0.209	neutral	None	None	None	None	I
Y/C	0.0874	likely_benign	0.0886	benign	-0.918	Destabilizing	0.975	D	0.222	neutral	N	0.494231797	None	None	I
Y/D	0.1473	likely_benign	0.1592	benign	-0.413	Destabilizing	0.642	D	0.363	neutral	N	0.520628965	None	None	I
Y/E	0.3951	ambiguous	0.4228	ambiguous	-0.325	Destabilizing	0.543	D	0.301	neutral	None	None	None	None	I
Y/F	0.0812	likely_benign	0.0861	benign	-0.737	Destabilizing	0.006	N	0.144	neutral	N	0.519935531	None	None	I
Y/G	0.2625	likely_benign	0.271	benign	-2.204	Highly Destabilizing	0.828	D	0.347	neutral	None	None	None	None	I
Y/H	0.1079	likely_benign	0.1152	benign	-0.835	Destabilizing	0.927	D	0.331	neutral	N	0.442245539	None	None	I
Y/I	0.197	likely_benign	0.2093	benign	-0.929	Destabilizing	0.031	N	0.175	neutral	None	None	None	None	I
Y/K	0.3447	ambiguous	0.3563	ambiguous	-1.064	Destabilizing	0.543	D	0.328	neutral	None	None	None	None	I
Y/L	0.2456	likely_benign	0.2605	benign	-0.929	Destabilizing	0.003	N	0.135	neutral	None	None	None	None	I
Y/M	0.3557	ambiguous	0.3845	ambiguous	-0.787	Destabilizing	0.893	D	0.283	neutral	None	None	None	None	I
Y/N	0.0968	likely_benign	0.1025	benign	-1.414	Destabilizing	0.784	D	0.375	neutral	N	0.520455606	None	None	I
Y/P	0.8703	likely_pathogenic	0.8466	pathogenic	-1.24	Destabilizing	0.981	D	0.357	neutral	None	None	None	None	I
Y/Q	0.2566	likely_benign	0.2726	benign	-1.243	Destabilizing	0.085	N	0.157	neutral	None	None	None	None	I
Y/R	0.2271	likely_benign	0.2373	benign	-0.819	Destabilizing	0.704	D	0.374	neutral	None	None	None	None	I
Y/S	0.0914	likely_benign	0.1019	benign	-1.924	Destabilizing	0.473	N	0.284	neutral	N	0.487169752	None	None	I
Y/T	0.1613	likely_benign	0.1734	benign	-1.728	Destabilizing	0.031	N	0.221	neutral	None	None	None	None	I
Y/V	0.1613	likely_benign	0.175	benign	-1.24	Destabilizing	0.013	N	0.127	neutral	None	None	None	None	I
Y/W	0.4208	ambiguous	0.4193	ambiguous	-0.447	Destabilizing	0.981	D	0.352	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.