TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31071	93436;93437;93438	chr2:178548415;178548414;178548413	chr2:179413142;179413141;179413140
N2AB	29430	88513;88514;88515	chr2:178548415;178548414;178548413	chr2:179413142;179413141;179413140
N2A	28503	85732;85733;85734	chr2:178548415;178548414;178548413	chr2:179413142;179413141;179413140
N2B	22006	66241;66242;66243	chr2:178548415;178548414;178548413	chr2:179413142;179413141;179413140
Novex-1	22131	66616;66617;66618	chr2:178548415;178548414;178548413	chr2:179413142;179413141;179413140
Novex-2	22198	66817;66818;66819	chr2:178548415;178548414;178548413	chr2:179413142;179413141;179413140
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-114
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.8883
• 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
T/A	rs1321544592	-0.168	None	N	0.075	0.093	0.170165803431	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/A	rs1321544592	-0.168	None	N	0.075	0.093	0.170165803431	gnomAD-4.0.0	1.59114E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85804E-06	0	0
T/I	rs780080115	None	None	D	0.156	0.156	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
T/A	0.072	likely_benign	0.0754	benign	-0.295	Destabilizing	None	N	0.075	neutral	N	0.489257547	None	None	I
T/C	0.3331	likely_benign	0.3787	ambiguous	-0.331	Destabilizing	0.824	D	0.314	neutral	None	None	None	None	I
T/D	0.4506	ambiguous	0.4795	ambiguous	0.183	Stabilizing	0.149	N	0.344	neutral	None	None	None	None	I
T/E	0.3737	ambiguous	0.4069	ambiguous	0.11	Stabilizing	0.149	N	0.276	neutral	None	None	None	None	I
T/F	0.2084	likely_benign	0.2272	benign	-0.771	Destabilizing	0.38	N	0.323	neutral	None	None	None	None	I
T/G	0.1464	likely_benign	0.1551	benign	-0.422	Destabilizing	0.035	N	0.265	neutral	None	None	None	None	I
T/H	0.2338	likely_benign	0.2482	benign	-0.6	Destabilizing	0.935	D	0.277	neutral	None	None	None	None	I
T/I	0.1134	likely_benign	0.129	benign	-0.083	Destabilizing	None	N	0.156	neutral	D	0.526295782	None	None	I
T/K	0.2949	likely_benign	0.3343	benign	-0.382	Destabilizing	0.149	N	0.291	neutral	None	None	None	None	I
T/L	0.0746	likely_benign	0.0821	benign	-0.083	Destabilizing	0.012	N	0.316	neutral	None	None	None	None	I
T/M	0.0855	likely_benign	0.0937	benign	-0.07	Destabilizing	0.38	N	0.319	neutral	None	None	None	None	I
T/N	0.0998	likely_benign	0.1019	benign	-0.179	Destabilizing	0.117	N	0.273	neutral	N	0.443869187	None	None	I
T/P	0.058	likely_benign	0.0603	benign	-0.126	Destabilizing	0.484	N	0.344	neutral	N	0.449584438	None	None	I
T/Q	0.2245	likely_benign	0.2402	benign	-0.379	Destabilizing	0.555	D	0.345	neutral	None	None	None	None	I
T/R	0.2738	likely_benign	0.3192	benign	-0.079	Destabilizing	0.38	N	0.357	neutral	None	None	None	None	I
T/S	0.0819	likely_benign	0.0828	benign	-0.388	Destabilizing	0.002	N	0.073	neutral	N	0.412276843	None	None	I
T/V	0.1025	likely_benign	0.1099	benign	-0.126	Destabilizing	0.012	N	0.259	neutral	None	None	None	None	I
T/W	0.567	likely_pathogenic	0.639	pathogenic	-0.804	Destabilizing	0.935	D	0.33	neutral	None	None	None	None	I
T/Y	0.2736	likely_benign	0.302	benign	-0.513	Destabilizing	0.555	D	0.305	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.