TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20117	60574;60575;60576	chr2:178591376;178591375;178591374	chr2:179456103;179456102;179456101
N2AB	18476	55651;55652;55653	chr2:178591376;178591375;178591374	chr2:179456103;179456102;179456101
N2A	17549	52870;52871;52872	chr2:178591376;178591375;178591374	chr2:179456103;179456102;179456101
N2B	11052	33379;33380;33381	chr2:178591376;178591375;178591374	chr2:179456103;179456102;179456101
Novex-1	11177	33754;33755;33756	chr2:178591376;178591375;178591374	chr2:179456103;179456102;179456101
Novex-2	11244	33955;33956;33957	chr2:178591376;178591375;178591374	chr2:179456103;179456102;179456101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-120
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.4192
• 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
S/R	rs527297991	None	0.055	N	0.403	0.141	0.289098819767	gnomAD-4.0.0	6.84563E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99912E-07	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
S/A	0.066	likely_benign	0.0651	benign	-0.294	Destabilizing	0.007	N	0.207	neutral	None	None	None	None	N
S/C	0.0695	likely_benign	0.0749	benign	-0.243	Destabilizing	0.295	N	0.331	neutral	N	0.488231359	None	None	N
S/D	0.1525	likely_benign	0.1536	benign	-0.033	Destabilizing	0.016	N	0.199	neutral	None	None	None	None	N
S/E	0.1695	likely_benign	0.1726	benign	-0.15	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
S/F	0.0967	likely_benign	0.098	benign	-1.027	Destabilizing	0.072	N	0.445	neutral	None	None	None	None	N
S/G	0.0784	likely_benign	0.0793	benign	-0.344	Destabilizing	0.012	N	0.223	neutral	N	0.443115117	None	None	N
S/H	0.1176	likely_benign	0.1212	benign	-0.832	Destabilizing	0.214	N	0.323	neutral	None	None	None	None	N
S/I	0.0609	likely_benign	0.064	benign	-0.291	Destabilizing	None	N	0.263	neutral	N	0.465567903	None	None	N
S/K	0.163	likely_benign	0.1632	benign	-0.405	Destabilizing	0.016	N	0.216	neutral	None	None	None	None	N
S/L	0.0617	likely_benign	0.0633	benign	-0.291	Destabilizing	0.002	N	0.261	neutral	None	None	None	None	N
S/M	0.0919	likely_benign	0.0903	benign	-0.023	Destabilizing	0.003	N	0.267	neutral	None	None	None	None	N
S/N	0.0603	likely_benign	0.061	benign	-0.111	Destabilizing	None	N	0.182	neutral	N	0.422393129	None	None	N
S/P	0.447	ambiguous	0.443	ambiguous	-0.268	Destabilizing	0.136	N	0.388	neutral	None	None	None	None	N
S/Q	0.1573	likely_benign	0.1581	benign	-0.398	Destabilizing	0.072	N	0.206	neutral	None	None	None	None	N
S/R	0.152	likely_benign	0.156	benign	-0.173	Destabilizing	0.055	N	0.403	neutral	N	0.425817436	None	None	N
S/T	0.055	likely_benign	0.0558	benign	-0.226	Destabilizing	None	N	0.122	neutral	N	0.453830756	None	None	N
S/V	0.0733	likely_benign	0.075	benign	-0.268	Destabilizing	None	N	0.201	neutral	None	None	None	None	N
S/W	0.1874	likely_benign	0.1895	benign	-1.067	Destabilizing	0.864	D	0.408	neutral	None	None	None	None	N
S/Y	0.0973	likely_benign	0.0984	benign	-0.773	Destabilizing	0.356	N	0.46	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.