TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26339	79240;79241;79242	chr2:178567117;178567116;178567115	chr2:179431844;179431843;179431842
N2AB	24698	74317;74318;74319	chr2:178567117;178567116;178567115	chr2:179431844;179431843;179431842
N2A	23771	71536;71537;71538	chr2:178567117;178567116;178567115	chr2:179431844;179431843;179431842
N2B	17274	52045;52046;52047	chr2:178567117;178567116;178567115	chr2:179431844;179431843;179431842
Novex-1	17399	52420;52421;52422	chr2:178567117;178567116;178567115	chr2:179431844;179431843;179431842
Novex-2	17466	52621;52622;52623	chr2:178567117;178567116;178567115	chr2:179431844;179431843;179431842
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-79
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.5719
• 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
S/L	None	None	0.193	N	0.273	0.184	0.42069145522	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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
S/A	0.0738	likely_benign	0.0691	benign	-0.346	Destabilizing	0.001	N	0.093	neutral	N	0.455736832	None	None	I
S/C	0.1545	likely_benign	0.1454	benign	-0.256	Destabilizing	0.944	D	0.333	neutral	None	None	None	None	I
S/D	0.4368	ambiguous	0.4273	ambiguous	-0.049	Destabilizing	0.388	N	0.195	neutral	None	None	None	None	I
S/E	0.5399	ambiguous	0.5259	ambiguous	-0.102	Destabilizing	0.116	N	0.199	neutral	None	None	None	None	I
S/F	0.3371	likely_benign	0.331	benign	-0.648	Destabilizing	0.818	D	0.331	neutral	None	None	None	None	I
S/G	0.0763	likely_benign	0.0774	benign	-0.542	Destabilizing	0.116	N	0.218	neutral	None	None	None	None	I
S/H	0.4166	ambiguous	0.411	ambiguous	-1.045	Destabilizing	0.818	D	0.339	neutral	None	None	None	None	I
S/I	0.3358	likely_benign	0.3074	benign	0.049	Stabilizing	0.527	D	0.349	neutral	None	None	None	None	I
S/K	0.6381	likely_pathogenic	0.6226	pathogenic	-0.696	Destabilizing	0.241	N	0.197	neutral	None	None	None	None	I
S/L	0.1231	likely_benign	0.1194	benign	0.049	Stabilizing	0.193	N	0.273	neutral	N	0.508837811	None	None	I
S/M	0.2315	likely_benign	0.2185	benign	0.207	Stabilizing	0.818	D	0.337	neutral	None	None	None	None	I
S/N	0.1338	likely_benign	0.1307	benign	-0.441	Destabilizing	0.388	N	0.238	neutral	None	None	None	None	I
S/P	0.1049	likely_benign	0.1036	benign	-0.05	Destabilizing	0.001	N	0.151	neutral	N	0.47478674	None	None	I
S/Q	0.4748	ambiguous	0.4667	ambiguous	-0.621	Destabilizing	0.024	N	0.154	neutral	None	None	None	None	I
S/R	0.6082	likely_pathogenic	0.6181	pathogenic	-0.515	Destabilizing	0.388	N	0.349	neutral	None	None	None	None	I
S/T	0.0889	likely_benign	0.0853	benign	-0.475	Destabilizing	0.001	N	0.117	neutral	N	0.439903375	None	None	I
S/V	0.2479	likely_benign	0.2322	benign	-0.05	Destabilizing	0.241	N	0.277	neutral	None	None	None	None	I
S/W	0.4809	ambiguous	0.4841	ambiguous	-0.686	Destabilizing	0.981	D	0.406	neutral	None	None	None	None	I
S/Y	0.3183	likely_benign	0.3087	benign	-0.422	Destabilizing	0.932	D	0.331	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.