TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20176	60751;60752;60753	chr2:178591199;178591198;178591197	chr2:179455926;179455925;179455924
N2AB	18535	55828;55829;55830	chr2:178591199;178591198;178591197	chr2:179455926;179455925;179455924
N2A	17608	53047;53048;53049	chr2:178591199;178591198;178591197	chr2:179455926;179455925;179455924
N2B	11111	33556;33557;33558	chr2:178591199;178591198;178591197	chr2:179455926;179455925;179455924
Novex-1	11236	33931;33932;33933	chr2:178591199;178591198;178591197	chr2:179455926;179455925;179455924
Novex-2	11303	34132;34133;34134	chr2:178591199;178591198;178591197	chr2:179455926;179455925;179455924
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-34
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2716
• 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	None	None	0.826	N	0.437	0.124	0.181679512989	gnomAD-4.0.0	1.59199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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	0.0783	likely_benign	0.0815	benign	-0.665	Destabilizing	0.826	D	0.437	neutral	N	0.473274082	None	None	N
T/C	0.3254	likely_benign	0.3062	benign	-0.432	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
T/D	0.4129	ambiguous	0.4636	ambiguous	-0.235	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
T/E	0.2403	likely_benign	0.2657	benign	-0.201	Destabilizing	0.969	D	0.595	neutral	None	None	None	None	N
T/F	0.2877	likely_benign	0.3156	benign	-0.57	Destabilizing	0.982	D	0.649	neutral	None	None	None	None	N
T/G	0.2326	likely_benign	0.242	benign	-0.964	Destabilizing	0.969	D	0.583	neutral	None	None	None	None	N
T/H	0.2999	likely_benign	0.3449	ambiguous	-1.299	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
T/I	0.1239	likely_benign	0.1184	benign	0.049	Stabilizing	0.061	N	0.312	neutral	N	0.444105968	None	None	N
T/K	0.169	likely_benign	0.1884	benign	-0.795	Destabilizing	0.959	D	0.579	neutral	N	0.470599136	None	None	N
T/L	0.0929	likely_benign	0.094	benign	0.049	Stabilizing	0.579	D	0.366	neutral	None	None	None	None	N
T/M	0.0884	likely_benign	0.0886	benign	0.146	Stabilizing	0.579	D	0.368	neutral	None	None	None	None	N
T/N	0.1629	likely_benign	0.1809	benign	-0.78	Destabilizing	0.997	D	0.542	neutral	None	None	None	None	N
T/P	0.3642	ambiguous	0.4524	ambiguous	-0.155	Destabilizing	0.996	D	0.601	neutral	N	0.422711976	None	None	N
T/Q	0.2032	likely_benign	0.2221	benign	-0.816	Destabilizing	0.991	D	0.579	neutral	None	None	None	None	N
T/R	0.1431	likely_benign	0.1722	benign	-0.705	Destabilizing	0.988	D	0.593	neutral	N	0.4783919	None	None	N
T/S	0.1178	likely_benign	0.1266	benign	-1.008	Destabilizing	0.959	D	0.499	neutral	N	0.449109143	None	None	N
T/V	0.0963	likely_benign	0.0847	benign	-0.155	Destabilizing	0.079	N	0.24	neutral	None	None	None	None	N
T/W	0.6493	likely_pathogenic	0.7074	pathogenic	-0.595	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
T/Y	0.336	likely_benign	0.3778	ambiguous	-0.346	Destabilizing	0.997	D	0.638	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.