TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7461	22606;22607;22608	chr2:178722406;178722405;178722404	chr2:179587133;179587132;179587131
N2AB	7144	21655;21656;21657	chr2:178722406;178722405;178722404	chr2:179587133;179587132;179587131
N2A	6217	18874;18875;18876	chr2:178722406;178722405;178722404	chr2:179587133;179587132;179587131
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-59
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.909
• 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
D/E	rs376383610	None	0.551	N	0.331	0.043	0.223847106136	gnomAD-4.0.0	1.36872E-06	None	None	None	None	N	None	0	0	None	0	5.04159E-05	None	0	0	0	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
D/A	0.3173	likely_benign	0.3108	benign	-0.271	Destabilizing	0.811	D	0.332	neutral	N	0.443533618	None	None	N
D/C	0.8689	likely_pathogenic	0.8563	pathogenic	0.114	Stabilizing	0.998	D	0.275	neutral	None	None	None	None	N
D/E	0.2517	likely_benign	0.2533	benign	-0.339	Destabilizing	0.551	D	0.331	neutral	N	0.462444666	None	None	N
D/F	0.8386	likely_pathogenic	0.8178	pathogenic	-0.251	Destabilizing	1.0	D	0.279	neutral	None	None	None	None	N
D/G	0.2308	likely_benign	0.2265	benign	-0.479	Destabilizing	0.019	N	0.167	neutral	N	0.499522974	None	None	N
D/H	0.5403	ambiguous	0.5123	ambiguous	-0.2	Destabilizing	0.995	D	0.267	neutral	N	0.521418398	None	None	N
D/I	0.7079	likely_pathogenic	0.6949	pathogenic	0.228	Stabilizing	0.999	D	0.302	neutral	None	None	None	None	N
D/K	0.5761	likely_pathogenic	0.5666	pathogenic	0.31	Stabilizing	0.98	D	0.321	neutral	None	None	None	None	N
D/L	0.6854	likely_pathogenic	0.6687	pathogenic	0.228	Stabilizing	0.99	D	0.356	neutral	None	None	None	None	N
D/M	0.8373	likely_pathogenic	0.8291	pathogenic	0.428	Stabilizing	1.0	D	0.269	neutral	None	None	None	None	N
D/N	0.1456	likely_benign	0.1538	benign	0.013	Stabilizing	0.903	D	0.256	neutral	N	0.49667467	None	None	N
D/P	0.6463	likely_pathogenic	0.6745	pathogenic	0.085	Stabilizing	0.933	D	0.304	neutral	None	None	None	None	N
D/Q	0.5453	ambiguous	0.5464	ambiguous	0.055	Stabilizing	0.769	D	0.18	neutral	None	None	None	None	N
D/R	0.6054	likely_pathogenic	0.5935	pathogenic	0.417	Stabilizing	0.236	N	0.236	neutral	None	None	None	None	N
D/S	0.2115	likely_benign	0.2249	benign	-0.088	Destabilizing	0.518	D	0.193	neutral	None	None	None	None	N
D/T	0.4428	ambiguous	0.442	ambiguous	0.074	Stabilizing	0.86	D	0.322	neutral	None	None	None	None	N
D/V	0.4935	ambiguous	0.4696	ambiguous	0.085	Stabilizing	0.989	D	0.34	neutral	N	0.510662687	None	None	N
D/W	0.942	likely_pathogenic	0.9294	pathogenic	-0.139	Destabilizing	1.0	D	0.304	neutral	None	None	None	None	N
D/Y	0.4596	ambiguous	0.4214	ambiguous	-0.019	Destabilizing	0.999	D	0.281	neutral	N	0.488441488	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.