TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22723	68392;68393;68394	chr2:178578863;178578862;178578861	chr2:179443590;179443589;179443588
N2AB	21082	63469;63470;63471	chr2:178578863;178578862;178578861	chr2:179443590;179443589;179443588
N2A	20155	60688;60689;60690	chr2:178578863;178578862;178578861	chr2:179443590;179443589;179443588
N2B	13658	41197;41198;41199	chr2:178578863;178578862;178578861	chr2:179443590;179443589;179443588
Novex-1	13783	41572;41573;41574	chr2:178578863;178578862;178578861	chr2:179443590;179443589;179443588
Novex-2	13850	41773;41774;41775	chr2:178578863;178578862;178578861	chr2:179443590;179443589;179443588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-52
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.4659
• 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
K/R	rs2154175020	None	0.032	N	0.371	0.084	0.235038932564	gnomAD-4.0.0	4.77791E-06	None	None	None	None	N	None	0	0	None	0	8.32963E-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
K/A	0.7269	likely_pathogenic	0.8396	pathogenic	-0.188	Destabilizing	0.86	D	0.601	neutral	None	None	None	None	N
K/C	0.8597	likely_pathogenic	0.914	pathogenic	-0.31	Destabilizing	0.998	D	0.702	prob.neutral	None	None	None	None	N
K/D	0.9271	likely_pathogenic	0.9613	pathogenic	0.169	Stabilizing	0.956	D	0.542	neutral	None	None	None	None	N
K/E	0.6406	likely_pathogenic	0.8148	pathogenic	0.194	Stabilizing	0.822	D	0.536	neutral	N	0.455238187	None	None	N
K/F	0.9561	likely_pathogenic	0.9723	pathogenic	-0.372	Destabilizing	0.956	D	0.653	neutral	None	None	None	None	N
K/G	0.8733	likely_pathogenic	0.9239	pathogenic	-0.405	Destabilizing	0.956	D	0.514	neutral	None	None	None	None	N
K/H	0.5796	likely_pathogenic	0.6455	pathogenic	-0.7	Destabilizing	0.994	D	0.527	neutral	None	None	None	None	N
K/I	0.6034	likely_pathogenic	0.7151	pathogenic	0.311	Stabilizing	0.89	D	0.651	neutral	N	0.486697244	None	None	N
K/L	0.6563	likely_pathogenic	0.7603	pathogenic	0.311	Stabilizing	0.514	D	0.585	neutral	None	None	None	None	N
K/M	0.532	ambiguous	0.6737	pathogenic	0.13	Stabilizing	0.559	D	0.559	neutral	None	None	None	None	N
K/N	0.833	likely_pathogenic	0.9097	pathogenic	0.112	Stabilizing	0.942	D	0.493	neutral	N	0.466088866	None	None	N
K/P	0.8602	likely_pathogenic	0.9165	pathogenic	0.173	Stabilizing	0.978	D	0.546	neutral	None	None	None	None	N
K/Q	0.3324	likely_benign	0.4368	ambiguous	-0.028	Destabilizing	0.942	D	0.496	neutral	N	0.491409631	None	None	N
K/R	0.0862	likely_benign	0.0847	benign	-0.102	Destabilizing	0.032	N	0.371	neutral	N	0.482963506	None	None	N
K/S	0.8252	likely_pathogenic	0.9018	pathogenic	-0.433	Destabilizing	0.86	D	0.532	neutral	None	None	None	None	N
K/T	0.4842	ambiguous	0.6472	pathogenic	-0.243	Destabilizing	0.942	D	0.502	neutral	N	0.506781728	None	None	N
K/V	0.6314	likely_pathogenic	0.7103	pathogenic	0.173	Stabilizing	0.754	D	0.531	neutral	None	None	None	None	N
K/W	0.9358	likely_pathogenic	0.9533	pathogenic	-0.358	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.8811	likely_pathogenic	0.915	pathogenic	-0.012	Destabilizing	0.978	D	0.627	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.