TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23448	70567;70568;70569	chr2:178575790;178575789;178575788	chr2:179440517;179440516;179440515
N2AB	21807	65644;65645;65646	chr2:178575790;178575789;178575788	chr2:179440517;179440516;179440515
N2A	20880	62863;62864;62865	chr2:178575790;178575789;178575788	chr2:179440517;179440516;179440515
N2B	14383	43372;43373;43374	chr2:178575790;178575789;178575788	chr2:179440517;179440516;179440515
Novex-1	14508	43747;43748;43749	chr2:178575790;178575789;178575788	chr2:179440517;179440516;179440515
Novex-2	14575	43948;43949;43950	chr2:178575790;178575789;178575788	chr2:179440517;179440516;179440515
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: Fn3-58
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2079
• 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	0.371	N	0.441	0.228	0.151104730317	gnomAD-4.0.0	1.59277E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	0	0	0
T/R	None	None	0.999	N	0.455	0.352	0.568465717781	gnomAD-4.0.0	1.59278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86218E-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	0.1177	likely_benign	0.143	benign	-0.836	Destabilizing	0.371	N	0.441	neutral	N	0.487465712	None	None	N
T/C	0.3666	ambiguous	0.419	ambiguous	-0.603	Destabilizing	0.227	N	0.398	neutral	None	None	None	None	N
T/D	0.4115	ambiguous	0.4492	ambiguous	-0.547	Destabilizing	0.996	D	0.453	neutral	None	None	None	None	N
T/E	0.446	ambiguous	0.5024	ambiguous	-0.56	Destabilizing	0.996	D	0.441	neutral	None	None	None	None	N
T/F	0.453	ambiguous	0.5267	ambiguous	-1.094	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
T/G	0.1592	likely_benign	0.1691	benign	-1.056	Destabilizing	0.999	D	0.478	neutral	None	None	None	None	N
T/H	0.2703	likely_benign	0.2951	benign	-1.426	Destabilizing	1.0	D	0.517	neutral	None	None	None	None	N
T/I	0.4976	ambiguous	0.6079	pathogenic	-0.345	Destabilizing	0.986	D	0.422	neutral	N	0.513091612	None	None	N
T/K	0.2216	likely_benign	0.2552	benign	-0.675	Destabilizing	0.997	D	0.413	neutral	N	0.521986041	None	None	N
T/L	0.1671	likely_benign	0.2055	benign	-0.345	Destabilizing	0.794	D	0.432	neutral	None	None	None	None	N
T/M	0.1437	likely_benign	0.1696	benign	0.078	Stabilizing	0.918	D	0.393	neutral	None	None	None	None	N
T/N	0.1263	likely_benign	0.1422	benign	-0.65	Destabilizing	0.996	D	0.423	neutral	None	None	None	None	N
T/P	0.6866	likely_pathogenic	0.7643	pathogenic	-0.478	Destabilizing	0.995	D	0.456	neutral	N	0.521485403	None	None	N
T/Q	0.2189	likely_benign	0.2368	benign	-0.929	Destabilizing	0.994	D	0.439	neutral	None	None	None	None	N
T/R	0.1912	likely_benign	0.2244	benign	-0.404	Destabilizing	0.999	D	0.455	neutral	N	0.520023171	None	None	N
T/S	0.0817	likely_benign	0.0844	benign	-0.899	Destabilizing	0.74	D	0.45	neutral	N	0.471882507	None	None	N
T/V	0.3233	likely_benign	0.4012	ambiguous	-0.478	Destabilizing	0.951	D	0.398	neutral	None	None	None	None	N
T/W	0.7608	likely_pathogenic	0.8088	pathogenic	-1.005	Destabilizing	1.0	D	0.544	neutral	None	None	None	None	N
T/Y	0.4563	ambiguous	0.5199	ambiguous	-0.743	Destabilizing	0.999	D	0.541	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.