TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6810	20653;20654;20655	chr2:178725894;178725893;178725892	chr2:179590621;179590620;179590619
N2AB	6493	19702;19703;19704	chr2:178725894;178725893;178725892	chr2:179590621;179590620;179590619
N2A	5566	16921;16922;16923	chr2:178725894;178725893;178725892	chr2:179590621;179590620;179590619
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-52
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4123
• 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
A/T	None	None	0.001	N	0.1	0.09	0.0482279557977	gnomAD-4.0.0	6.84492E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99716E-07	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
A/C	0.4399	ambiguous	0.4896	ambiguous	-0.687	Destabilizing	0.94	D	0.408	neutral	None	None	None	None	N
A/D	0.3008	likely_benign	0.3021	benign	-0.42	Destabilizing	0.418	N	0.45	neutral	None	None	None	None	N
A/E	0.2793	likely_benign	0.2877	benign	-0.564	Destabilizing	0.351	N	0.403	neutral	N	0.394414306	None	None	N
A/F	0.1959	likely_benign	0.2028	benign	-0.866	Destabilizing	0.716	D	0.499	neutral	None	None	None	None	N
A/G	0.1696	likely_benign	0.1587	benign	-0.375	Destabilizing	0.101	N	0.29	neutral	N	0.449211583	None	None	N
A/H	0.3845	ambiguous	0.4004	ambiguous	-0.436	Destabilizing	0.836	D	0.463	neutral	None	None	None	None	N
A/I	0.1332	likely_benign	0.1431	benign	-0.263	Destabilizing	0.129	N	0.385	neutral	None	None	None	None	N
A/K	0.4859	ambiguous	0.5164	ambiguous	-0.626	Destabilizing	0.264	N	0.406	neutral	None	None	None	None	N
A/L	0.1174	likely_benign	0.1223	benign	-0.263	Destabilizing	0.022	N	0.332	neutral	None	None	None	None	N
A/M	0.1514	likely_benign	0.1614	benign	-0.266	Destabilizing	0.061	N	0.255	neutral	None	None	None	None	N
A/N	0.1901	likely_benign	0.1883	benign	-0.258	Destabilizing	0.264	N	0.479	neutral	None	None	None	None	N
A/P	0.662	likely_pathogenic	0.6476	pathogenic	-0.236	Destabilizing	0.523	D	0.431	neutral	N	0.451809171	None	None	N
A/Q	0.3359	likely_benign	0.338	benign	-0.535	Destabilizing	0.716	D	0.454	neutral	None	None	None	None	N
A/R	0.424	ambiguous	0.4543	ambiguous	-0.172	Destabilizing	0.716	D	0.454	neutral	None	None	None	None	N
A/S	0.0788	likely_benign	0.0787	benign	-0.496	Destabilizing	0.003	N	0.121	neutral	N	0.369190575	None	None	N
A/T	0.0637	likely_benign	0.0654	benign	-0.556	Destabilizing	0.001	N	0.1	neutral	N	0.355837276	None	None	N
A/V	0.0897	likely_benign	0.0921	benign	-0.236	Destabilizing	0.001	N	0.111	neutral	N	0.383872026	None	None	N
A/W	0.6462	likely_pathogenic	0.6372	pathogenic	-1.028	Destabilizing	0.983	D	0.513	neutral	None	None	None	None	N
A/Y	0.3309	likely_benign	0.3391	benign	-0.659	Destabilizing	0.836	D	0.487	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.