TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29523	88792;88793;88794	chr2:178554892;178554891;178554890	chr2:179419619;179419618;179419617
N2AB	27882	83869;83870;83871	chr2:178554892;178554891;178554890	chr2:179419619;179419618;179419617
N2A	26955	81088;81089;81090	chr2:178554892;178554891;178554890	chr2:179419619;179419618;179419617
N2B	20458	61597;61598;61599	chr2:178554892;178554891;178554890	chr2:179419619;179419618;179419617
Novex-1	20583	61972;61973;61974	chr2:178554892;178554891;178554890	chr2:179419619;179419618;179419617
Novex-2	20650	62173;62174;62175	chr2:178554892;178554891;178554890	chr2:179419619;179419618;179419617
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: Ig-146
• Domain position: 80
• Structural Position: 168
• Q(SASA): 0.5588
• 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/P	None	None	0.988	D	0.608	0.517	0.424194796918	gnomAD-4.0.0	1.59113E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85783E-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	0.079	likely_benign	0.0755	benign	-0.324	Destabilizing	0.061	N	0.123	neutral	N	0.502179277	None	None	I
S/C	0.1133	likely_benign	0.1084	benign	-0.328	Destabilizing	0.046	N	0.219	neutral	None	None	None	None	I
S/D	0.5387	ambiguous	0.4774	ambiguous	0.304	Stabilizing	0.969	D	0.475	neutral	None	None	None	None	I
S/E	0.5498	ambiguous	0.4933	ambiguous	0.217	Stabilizing	0.969	D	0.462	neutral	None	None	None	None	I
S/F	0.1618	likely_benign	0.1471	benign	-0.879	Destabilizing	0.964	D	0.589	neutral	None	None	None	None	I
S/G	0.1286	likely_benign	0.1224	benign	-0.445	Destabilizing	0.863	D	0.456	neutral	None	None	None	None	I
S/H	0.3076	likely_benign	0.2774	benign	-0.922	Destabilizing	0.982	D	0.57	neutral	None	None	None	None	I
S/I	0.1741	likely_benign	0.1608	benign	-0.139	Destabilizing	0.969	D	0.581	neutral	None	None	None	None	I
S/K	0.5487	ambiguous	0.4832	ambiguous	-0.427	Destabilizing	0.969	D	0.428	neutral	None	None	None	None	I
S/L	0.1059	likely_benign	0.0995	benign	-0.139	Destabilizing	0.826	D	0.509	neutral	N	0.508798605	None	None	I
S/M	0.1926	likely_benign	0.1862	benign	-0.002	Destabilizing	0.997	D	0.568	neutral	None	None	None	None	I
S/N	0.1791	likely_benign	0.1698	benign	-0.179	Destabilizing	0.99	D	0.499	neutral	None	None	None	None	I
S/P	0.8959	likely_pathogenic	0.8439	pathogenic	-0.171	Destabilizing	0.988	D	0.608	neutral	D	0.527827083	None	None	I
S/Q	0.4558	ambiguous	0.4134	ambiguous	-0.402	Destabilizing	0.997	D	0.509	neutral	None	None	None	None	I
S/R	0.4559	ambiguous	0.3982	ambiguous	-0.248	Destabilizing	0.991	D	0.606	neutral	None	None	None	None	I
S/T	0.0731	likely_benign	0.0722	benign	-0.294	Destabilizing	0.826	D	0.43	neutral	N	0.448150004	None	None	I
S/V	0.1542	likely_benign	0.1456	benign	-0.171	Destabilizing	0.939	D	0.519	neutral	None	None	None	None	I
S/W	0.3473	ambiguous	0.3081	benign	-0.889	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	I
S/Y	0.1812	likely_benign	0.1646	benign	-0.6	Destabilizing	0.17	N	0.411	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.