TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34083	102472;102473;102474	chr2:178534368;178534367;178534366	chr2:179399095;179399094;179399093
N2AB	32442	97549;97550;97551	chr2:178534368;178534367;178534366	chr2:179399095;179399094;179399093
N2A	31515	94768;94769;94770	chr2:178534368;178534367;178534366	chr2:179399095;179399094;179399093
N2B	25018	75277;75278;75279	chr2:178534368;178534367;178534366	chr2:179399095;179399094;179399093
Novex-1	25143	75652;75653;75654	chr2:178534368;178534367;178534366	chr2:179399095;179399094;179399093
Novex-2	25210	75853;75854;75855	chr2:178534368;178534367;178534366	chr2:179399095;179399094;179399093
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: Kinase-1
• Domain position: 271
• Q(SASA): 0.4839
• 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	None	None	None	N	None	0.096	0.152612264143	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
K/A	0.6293	likely_pathogenic	0.5864	pathogenic	0.016	Stabilizing	None	None	None	None	None	None	None	None	N
K/C	0.9307	likely_pathogenic	0.9294	pathogenic	-0.155	Destabilizing	None	None	None	None	None	None	None	None	N
K/D	0.7931	likely_pathogenic	0.799	pathogenic	0.052	Stabilizing	None	None	None	None	None	None	None	None	N
K/E	0.4931	ambiguous	0.4788	ambiguous	0.073	Stabilizing	None	None	None	None	N	0.427752436	None	None	N
K/F	0.9634	likely_pathogenic	0.9601	pathogenic	-0.103	Destabilizing	None	None	None	None	None	None	None	None	N
K/G	0.7668	likely_pathogenic	0.7511	pathogenic	-0.217	Destabilizing	None	None	None	None	None	None	None	None	N
K/H	0.5899	likely_pathogenic	0.5947	pathogenic	-0.562	Destabilizing	None	None	None	None	None	None	None	None	N
K/I	0.7864	likely_pathogenic	0.7724	pathogenic	0.557	Stabilizing	None	None	None	None	N	0.427405719	None	None	N
K/L	0.7659	likely_pathogenic	0.7463	pathogenic	0.557	Stabilizing	None	None	None	None	None	None	None	None	N
K/M	0.655	likely_pathogenic	0.6116	pathogenic	0.321	Stabilizing	None	None	None	None	None	None	None	None	N
K/N	0.7525	likely_pathogenic	0.7536	pathogenic	0.189	Stabilizing	None	None	None	None	N	0.427925794	None	None	N
K/P	0.9264	likely_pathogenic	0.9501	pathogenic	0.406	Stabilizing	None	None	None	None	None	None	None	None	N
K/Q	0.4021	ambiguous	0.3892	ambiguous	0.036	Stabilizing	None	None	None	None	N	0.427752436	None	None	N
K/R	0.1347	likely_benign	0.1394	benign	-0.142	Destabilizing	None	None	None	None	N	0.427752436	None	None	N
K/S	0.7473	likely_pathogenic	0.7273	pathogenic	-0.29	Destabilizing	None	None	None	None	None	None	None	None	N
K/T	0.4534	ambiguous	0.4265	ambiguous	-0.112	Destabilizing	None	None	None	None	N	0.427579078	None	None	N
K/V	0.7006	likely_pathogenic	0.69	pathogenic	0.406	Stabilizing	None	None	None	None	None	None	None	None	N
K/W	0.9572	likely_pathogenic	0.9526	pathogenic	-0.113	Destabilizing	None	None	None	None	None	None	None	None	N
K/Y	0.8965	likely_pathogenic	0.8873	pathogenic	0.234	Stabilizing	None	None	None	None	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.