TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9344	28255;28256;28257	chr2:178711206;178711205;178711204	chr2:179575933;179575932;179575931
N2AB	9027	27304;27305;27306	chr2:178711206;178711205;178711204	chr2:179575933;179575932;179575931
N2A	8100	24523;24524;24525	chr2:178711206;178711205;178711204	chr2:179575933;179575932;179575931
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-79
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.8872
• 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	rs1338895544	0.066	0.106	None	0.327	0.174	0.223146558224	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/R	rs1338895544	0.066	0.106	None	0.327	0.174	0.223146558224	gnomAD-4.0.0	6.84182E-07	None	None	None	None	N	None	0	2.23604E-05	None	0	0	None	0	0	0	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	0.149	likely_benign	0.1349	benign	-0.242	Destabilizing	0.007	N	0.199	neutral	None	None	None	None	N
S/C	0.1961	likely_benign	0.1751	benign	-0.248	Destabilizing	0.828	D	0.265	neutral	None	None	None	None	N
S/D	0.1661	likely_benign	0.204	benign	-0.017	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
S/E	0.3597	ambiguous	0.4298	ambiguous	-0.117	Destabilizing	0.016	N	0.285	neutral	None	None	None	None	N
S/F	0.2712	likely_benign	0.2504	benign	-0.814	Destabilizing	0.628	D	0.267	neutral	None	None	None	None	N
S/G	0.0823	likely_benign	0.0735	benign	-0.349	Destabilizing	None	N	0.083	neutral	None	None	None	None	N
S/H	0.2071	likely_benign	0.2461	benign	-0.824	Destabilizing	0.628	D	0.256	neutral	None	None	None	None	N
S/I	0.1904	likely_benign	0.1933	benign	-0.092	Destabilizing	0.295	N	0.313	neutral	None	None	None	None	N
S/K	0.4805	ambiguous	0.5713	pathogenic	-0.547	Destabilizing	0.072	N	0.222	neutral	None	None	None	None	N
S/L	0.1634	likely_benign	0.1391	benign	-0.092	Destabilizing	0.072	N	0.296	neutral	None	None	None	None	N
S/M	0.253	likely_benign	0.2447	benign	0.099	Stabilizing	0.628	D	0.265	neutral	None	None	None	None	N
S/N	0.1112	likely_benign	0.1099	benign	-0.235	Destabilizing	0.012	N	0.283	neutral	None	None	None	None	N
S/P	0.7213	likely_pathogenic	0.774	pathogenic	-0.114	Destabilizing	0.136	N	0.328	neutral	None	None	None	None	N
S/Q	0.3838	ambiguous	0.4398	ambiguous	-0.498	Destabilizing	0.136	N	0.227	neutral	None	None	None	None	N
S/R	0.429	ambiguous	0.5196	ambiguous	-0.292	Destabilizing	0.106	N	0.327	neutral	None	None	None	None	N
S/T	0.1312	likely_benign	0.1045	benign	-0.328	Destabilizing	0.024	N	0.269	neutral	None	None	None	None	N
S/V	0.2526	likely_benign	0.2406	benign	-0.114	Destabilizing	0.136	N	0.304	neutral	None	None	None	None	N
S/W	0.4318	ambiguous	0.4383	ambiguous	-0.851	Destabilizing	0.864	D	0.28	neutral	None	None	None	None	N
S/Y	0.2008	likely_benign	0.2163	benign	-0.571	Destabilizing	0.628	D	0.265	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.