TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6692	20299;20300;20301	chr2:178727291;178727290;178727289	chr2:179592018;179592017;179592016
N2AB	6375	19348;19349;19350	chr2:178727291;178727290;178727289	chr2:179592018;179592017;179592016
N2A	5448	16567;16568;16569	chr2:178727291;178727290;178727289	chr2:179592018;179592017;179592016
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-51
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.396
• 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/S	rs757056558	None	None	N	0.066	0.082	0.141422826196	gnomAD-4.0.0	6.84548E-07	None	None	None	None	N	None	2.99133E-05	0	None	0	0	None	0	0	0	0	0
A/T	rs757056558	-0.613	None	N	0.065	0.067	0.200317383148	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	9.31E-05	8.91E-06	0
A/T	rs757056558	-0.613	None	N	0.065	0.067	0.200317383148	gnomAD-4.0.0	8.21458E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.62219E-05	0	8.09808E-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
A/C	0.4169	ambiguous	0.4476	ambiguous	-0.86	Destabilizing	0.356	N	0.358	neutral	None	None	None	None	N
A/D	0.3165	likely_benign	0.3445	ambiguous	-0.673	Destabilizing	0.055	N	0.357	neutral	N	0.449056868	None	None	N
A/E	0.2818	likely_benign	0.3055	benign	-0.714	Destabilizing	0.038	N	0.335	neutral	None	None	None	None	N
A/F	0.2507	likely_benign	0.2498	benign	-0.666	Destabilizing	0.214	N	0.398	neutral	None	None	None	None	N
A/G	0.1214	likely_benign	0.121	benign	-0.77	Destabilizing	0.012	N	0.282	neutral	N	0.442477612	None	None	N
A/H	0.3849	ambiguous	0.4174	ambiguous	-0.771	Destabilizing	0.356	N	0.341	neutral	None	None	None	None	N
A/I	0.1773	likely_benign	0.1756	benign	-0.115	Destabilizing	None	N	0.205	neutral	None	None	None	None	N
A/K	0.4082	ambiguous	0.4532	ambiguous	-1.035	Destabilizing	0.038	N	0.337	neutral	None	None	None	None	N
A/L	0.1234	likely_benign	0.1225	benign	-0.115	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
A/M	0.1602	likely_benign	0.1654	benign	-0.305	Destabilizing	0.214	N	0.327	neutral	None	None	None	None	N
A/N	0.2067	likely_benign	0.2118	benign	-0.816	Destabilizing	0.038	N	0.355	neutral	None	None	None	None	N
A/P	0.54	ambiguous	0.5634	ambiguous	-0.219	Destabilizing	0.106	N	0.369	neutral	N	0.515647219	None	None	N
A/Q	0.3186	likely_benign	0.3391	benign	-0.935	Destabilizing	0.214	N	0.371	neutral	None	None	None	None	N
A/R	0.3331	likely_benign	0.3852	ambiguous	-0.68	Destabilizing	0.072	N	0.393	neutral	None	None	None	None	N
A/S	0.0743	likely_benign	0.0732	benign	-1.146	Destabilizing	None	N	0.066	neutral	N	0.377828701	None	None	N
A/T	0.0636	likely_benign	0.0629	benign	-1.08	Destabilizing	None	N	0.065	neutral	N	0.41507758	None	None	N
A/V	0.1176	likely_benign	0.1128	benign	-0.219	Destabilizing	0.004	N	0.267	neutral	N	0.462602168	None	None	N
A/W	0.5992	likely_pathogenic	0.646	pathogenic	-0.975	Destabilizing	0.864	D	0.423	neutral	None	None	None	None	N
A/Y	0.3776	ambiguous	0.4037	ambiguous	-0.565	Destabilizing	0.356	N	0.369	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.