TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23816	71671;71672;71673	chr2:178574686;178574685;178574684	chr2:179439413;179439412;179439411
N2AB	22175	66748;66749;66750	chr2:178574686;178574685;178574684	chr2:179439413;179439412;179439411
N2A	21248	63967;63968;63969	chr2:178574686;178574685;178574684	chr2:179439413;179439412;179439411
N2B	14751	44476;44477;44478	chr2:178574686;178574685;178574684	chr2:179439413;179439412;179439411
Novex-1	14876	44851;44852;44853	chr2:178574686;178574685;178574684	chr2:179439413;179439412;179439411
Novex-2	14943	45052;45053;45054	chr2:178574686;178574685;178574684	chr2:179439413;179439412;179439411
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-60
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.5494
• 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
A/T	None	None	None	N	0.139	0.066	0.411133732114	gnomAD-4.0.0	1.36883E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79926E-06	0	0
A/V	rs1270658068	None	0.03	N	0.251	0.097	0.514530392947	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
A/V	rs1270658068	None	0.03	N	0.251	0.097	0.514530392947	gnomAD-4.0.0	3.84561E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78842E-06	1.34138E-05	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
A/C	0.362	ambiguous	0.3337	benign	-0.817	Destabilizing	0.685	D	0.412	neutral	None	None	None	None	I
A/D	0.125	likely_benign	0.1134	benign	-0.413	Destabilizing	0.016	N	0.379	neutral	None	None	None	None	I
A/E	0.1196	likely_benign	0.1157	benign	-0.444	Destabilizing	None	N	0.105	neutral	N	0.334367846	None	None	I
A/F	0.3308	likely_benign	0.2856	benign	-0.66	Destabilizing	0.366	N	0.613	neutral	None	None	None	None	I
A/G	0.118	likely_benign	0.1062	benign	-0.776	Destabilizing	None	N	0.077	neutral	N	0.40502001	None	None	I
A/H	0.2914	likely_benign	0.2628	benign	-0.675	Destabilizing	0.366	N	0.502	neutral	None	None	None	None	I
A/I	0.1732	likely_benign	0.1585	benign	-0.105	Destabilizing	0.125	N	0.537	neutral	None	None	None	None	I
A/K	0.2235	likely_benign	0.2015	benign	-0.793	Destabilizing	0.039	N	0.401	neutral	None	None	None	None	I
A/L	0.1268	likely_benign	0.1226	benign	-0.105	Destabilizing	0.039	N	0.398	neutral	None	None	None	None	I
A/M	0.1746	likely_benign	0.1624	benign	-0.339	Destabilizing	0.366	N	0.414	neutral	None	None	None	None	I
A/N	0.1247	likely_benign	0.1099	benign	-0.616	Destabilizing	0.075	N	0.466	neutral	None	None	None	None	I
A/P	0.0887	likely_benign	0.0855	benign	-0.213	Destabilizing	0.11	N	0.51	neutral	N	0.441151382	None	None	I
A/Q	0.1769	likely_benign	0.1648	benign	-0.718	Destabilizing	0.039	N	0.524	neutral	None	None	None	None	I
A/R	0.2612	likely_benign	0.2421	benign	-0.479	Destabilizing	0.075	N	0.52	neutral	None	None	None	None	I
A/S	0.0699	likely_benign	0.0674	benign	-0.995	Destabilizing	0.012	N	0.328	neutral	N	0.408193601	None	None	I
A/T	0.0674	likely_benign	0.0661	benign	-0.91	Destabilizing	None	N	0.139	neutral	N	0.439785945	None	None	I
A/V	0.1004	likely_benign	0.0963	benign	-0.213	Destabilizing	0.03	N	0.251	neutral	N	0.458718422	None	None	I
A/W	0.6908	likely_pathogenic	0.6346	pathogenic	-0.935	Destabilizing	0.869	D	0.548	neutral	None	None	None	None	I
A/Y	0.377	ambiguous	0.3259	benign	-0.517	Destabilizing	0.366	N	0.586	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.