TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25647	77164;77165;77166	chr2:178569193;178569192;178569191	chr2:179433920;179433919;179433918
N2AB	24006	72241;72242;72243	chr2:178569193;178569192;178569191	chr2:179433920;179433919;179433918
N2A	23079	69460;69461;69462	chr2:178569193;178569192;178569191	chr2:179433920;179433919;179433918
N2B	16582	49969;49970;49971	chr2:178569193;178569192;178569191	chr2:179433920;179433919;179433918
Novex-1	16707	50344;50345;50346	chr2:178569193;178569192;178569191	chr2:179433920;179433919;179433918
Novex-2	16774	50545;50546;50547	chr2:178569193;178569192;178569191	chr2:179433920;179433919;179433918
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: Fn3-74
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5665
• 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
S/T	None	None	0.001	N	0.111	0.095	0.119812018005	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0687	likely_benign	0.0729	benign	-0.432	Destabilizing	None	N	0.113	neutral	N	0.395827311	None	None	N
S/C	0.2503	likely_benign	0.2682	benign	-0.483	Destabilizing	0.901	D	0.278	neutral	None	None	None	None	N
S/D	0.9633	likely_pathogenic	0.9574	pathogenic	0.487	Stabilizing	0.561	D	0.199	neutral	None	None	None	None	N
S/E	0.9622	likely_pathogenic	0.956	pathogenic	0.417	Stabilizing	0.561	D	0.217	neutral	None	None	None	None	N
S/F	0.6973	likely_pathogenic	0.6861	pathogenic	-0.923	Destabilizing	0.901	D	0.351	neutral	None	None	None	None	N
S/G	0.2393	likely_benign	0.2237	benign	-0.56	Destabilizing	0.209	N	0.251	neutral	None	None	None	None	N
S/H	0.8853	likely_pathogenic	0.8809	pathogenic	-0.839	Destabilizing	0.965	D	0.277	neutral	None	None	None	None	N
S/I	0.5047	ambiguous	0.4679	ambiguous	-0.223	Destabilizing	0.209	N	0.291	neutral	None	None	None	None	N
S/K	0.9869	likely_pathogenic	0.9851	pathogenic	-0.399	Destabilizing	0.561	D	0.214	neutral	None	None	None	None	N
S/L	0.3205	likely_benign	0.3099	benign	-0.223	Destabilizing	0.166	N	0.339	neutral	N	0.48731332	None	None	N
S/M	0.4113	ambiguous	0.403	ambiguous	-0.255	Destabilizing	0.901	D	0.274	neutral	None	None	None	None	N
S/N	0.5778	likely_pathogenic	0.5576	ambiguous	-0.227	Destabilizing	0.561	D	0.211	neutral	None	None	None	None	N
S/P	0.8366	likely_pathogenic	0.8259	pathogenic	-0.263	Destabilizing	0.662	D	0.312	neutral	N	0.516212075	None	None	N
S/Q	0.9022	likely_pathogenic	0.8979	pathogenic	-0.4	Destabilizing	0.901	D	0.242	neutral	None	None	None	None	N
S/R	0.9738	likely_pathogenic	0.9716	pathogenic	-0.189	Destabilizing	0.561	D	0.293	neutral	None	None	None	None	N
S/T	0.1558	likely_benign	0.156	benign	-0.361	Destabilizing	0.001	N	0.111	neutral	N	0.41458643	None	None	N
S/V	0.336	likely_benign	0.3355	benign	-0.263	Destabilizing	0.002	N	0.161	neutral	None	None	None	None	N
S/W	0.8708	likely_pathogenic	0.8597	pathogenic	-0.92	Destabilizing	0.991	D	0.329	neutral	None	None	None	None	N
S/Y	0.6936	likely_pathogenic	0.6635	pathogenic	-0.635	Destabilizing	0.965	D	0.342	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.