TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20917	62974;62975;62976	chr2:178588976;178588975;178588974	chr2:179453703;179453702;179453701
N2AB	19276	58051;58052;58053	chr2:178588976;178588975;178588974	chr2:179453703;179453702;179453701
N2A	18349	55270;55271;55272	chr2:178588976;178588975;178588974	chr2:179453703;179453702;179453701
N2B	11852	35779;35780;35781	chr2:178588976;178588975;178588974	chr2:179453703;179453702;179453701
Novex-1	11977	36154;36155;36156	chr2:178588976;178588975;178588974	chr2:179453703;179453702;179453701
Novex-2	12044	36355;36356;36357	chr2:178588976;178588975;178588974	chr2:179453703;179453702;179453701
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: Fn3-39
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.654
• 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	rs1052813873	None	None	N	0.087	0.047	0.141422826196	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs1052813873	None	None	N	0.087	0.047	0.141422826196	gnomAD-4.0.0	2.03009E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.20501E-06	4.69704E-05	0
T/S	None	None	None	N	0.091	0.049	0.0611884634855	gnomAD-4.0.0	1.36973E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79955E-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	0.0552	likely_benign	0.0569	benign	-0.33	Destabilizing	None	N	0.087	neutral	N	0.405849516	None	None	N
T/C	0.2903	likely_benign	0.295	benign	-0.216	Destabilizing	0.356	N	0.307	neutral	None	None	None	None	N
T/D	0.3659	ambiguous	0.3742	ambiguous	0.205	Stabilizing	0.016	N	0.255	neutral	None	None	None	None	N
T/E	0.3931	ambiguous	0.3898	ambiguous	0.122	Stabilizing	0.016	N	0.257	neutral	None	None	None	None	N
T/F	0.2699	likely_benign	0.277	benign	-0.862	Destabilizing	0.356	N	0.309	neutral	None	None	None	None	N
T/G	0.142	likely_benign	0.147	benign	-0.445	Destabilizing	0.016	N	0.252	neutral	None	None	None	None	N
T/H	0.243	likely_benign	0.2576	benign	-0.733	Destabilizing	0.214	N	0.288	neutral	None	None	None	None	N
T/I	0.2204	likely_benign	0.2211	benign	-0.151	Destabilizing	0.055	N	0.353	neutral	N	0.471882507	None	None	N
T/K	0.3237	likely_benign	0.3276	benign	-0.289	Destabilizing	0.016	N	0.259	neutral	None	None	None	None	N
T/L	0.113	likely_benign	0.1185	benign	-0.151	Destabilizing	0.016	N	0.261	neutral	None	None	None	None	N
T/M	0.0967	likely_benign	0.0976	benign	0.051	Stabilizing	0.628	D	0.317	neutral	None	None	None	None	N
T/N	0.0852	likely_benign	0.0898	benign	-0.065	Destabilizing	None	N	0.083	neutral	N	0.426475505	None	None	N
T/P	0.2953	likely_benign	0.2734	benign	-0.183	Destabilizing	0.106	N	0.356	neutral	N	0.467548549	None	None	N
T/Q	0.2527	likely_benign	0.2619	benign	-0.31	Destabilizing	0.072	N	0.349	neutral	None	None	None	None	N
T/R	0.286	likely_benign	0.2856	benign	-0.012	Destabilizing	0.072	N	0.314	neutral	None	None	None	None	N
T/S	0.0746	likely_benign	0.0749	benign	-0.283	Destabilizing	None	N	0.091	neutral	N	0.391648068	None	None	N
T/V	0.142	likely_benign	0.1443	benign	-0.183	Destabilizing	0.016	N	0.171	neutral	None	None	None	None	N
T/W	0.6352	likely_pathogenic	0.6444	pathogenic	-0.867	Destabilizing	0.864	D	0.31	neutral	None	None	None	None	N
T/Y	0.2651	likely_benign	0.2914	benign	-0.577	Destabilizing	0.628	D	0.303	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.