TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15158	45697;45698;45699	chr2:178621246;178621245;178621244	chr2:179485973;179485972;179485971
N2AB	13517	40774;40775;40776	chr2:178621246;178621245;178621244	chr2:179485973;179485972;179485971
N2A	12590	37993;37994;37995	chr2:178621246;178621245;178621244	chr2:179485973;179485972;179485971
N2B	6093	18502;18503;18504	chr2:178621246;178621245;178621244	chr2:179485973;179485972;179485971
Novex-1	6218	18877;18878;18879	chr2:178621246;178621245;178621244	chr2:179485973;179485972;179485971
Novex-2	6285	19078;19079;19080	chr2:178621246;178621245;178621244	chr2:179485973;179485972;179485971
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: Ig-103
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.4005
• 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/I	rs371879778	-0.07	None	N	0.19	0.117	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.24244E-04	0	None	0	0	None	3.27E-05	None	0	0	0
T/I	rs371879778	-0.07	None	N	0.19	0.117	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	7.25E-05	0	0	0	0	None	0	0	4.42E-05	0	0
T/I	rs371879778	-0.07	None	N	0.19	0.117	None	gnomAD-4.0.0	1.24058E-05	None	None	None	None	N	None	5.34817E-05	3.34627E-05	None	0	0	None	0	0	1.01772E-05	2.19698E-05	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	0.0832	likely_benign	0.09	benign	-0.443	Destabilizing	0.019	N	0.182	neutral	N	0.439474788	None	None	N
T/C	0.4628	ambiguous	0.3848	ambiguous	-0.321	Destabilizing	0.859	D	0.362	neutral	None	None	None	None	N
T/D	0.3019	likely_benign	0.3004	benign	0.202	Stabilizing	0.055	N	0.346	neutral	None	None	None	None	N
T/E	0.2041	likely_benign	0.2019	benign	0.153	Stabilizing	0.002	N	0.159	neutral	None	None	None	None	N
T/F	0.1952	likely_benign	0.189	benign	-0.685	Destabilizing	0.497	N	0.469	neutral	None	None	None	None	N
T/G	0.3046	likely_benign	0.2948	benign	-0.633	Destabilizing	0.104	N	0.343	neutral	None	None	None	None	N
T/H	0.2414	likely_benign	0.2337	benign	-0.872	Destabilizing	0.667	D	0.412	neutral	None	None	None	None	N
T/I	0.0756	likely_benign	0.0751	benign	-0.051	Destabilizing	None	N	0.19	neutral	N	0.423391183	None	None	N
T/K	0.1835	likely_benign	0.1633	benign	-0.505	Destabilizing	None	N	0.181	neutral	N	0.429483707	None	None	N
T/L	0.0752	likely_benign	0.0752	benign	-0.051	Destabilizing	0.009	N	0.266	neutral	None	None	None	None	N
T/M	0.069	likely_benign	0.0737	benign	0.061	Stabilizing	0.497	N	0.377	neutral	None	None	None	None	N
T/N	0.0927	likely_benign	0.1031	benign	-0.274	Destabilizing	0.22	N	0.221	neutral	None	None	None	None	N
T/P	0.0895	likely_benign	0.0958	benign	-0.151	Destabilizing	None	N	0.184	neutral	N	0.370947404	None	None	N
T/Q	0.1768	likely_benign	0.176	benign	-0.477	Destabilizing	0.124	N	0.364	neutral	None	None	None	None	N
T/R	0.1821	likely_benign	0.1684	benign	-0.231	Destabilizing	0.096	N	0.381	neutral	N	0.463912919	None	None	N
T/S	0.1192	likely_benign	0.1279	benign	-0.541	Destabilizing	0.042	N	0.205	neutral	N	0.470410249	None	None	N
T/V	0.0852	likely_benign	0.0857	benign	-0.151	Destabilizing	None	N	0.113	neutral	None	None	None	None	N
T/W	0.5838	likely_pathogenic	0.5427	ambiguous	-0.655	Destabilizing	0.958	D	0.41	neutral	None	None	None	None	N
T/Y	0.2594	likely_benign	0.239	benign	-0.407	Destabilizing	0.667	D	0.461	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.