TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19309	58150;58151;58152	chr2:178594569;178594568;178594567	chr2:179459296;179459295;179459294
N2AB	17668	53227;53228;53229	chr2:178594569;178594568;178594567	chr2:179459296;179459295;179459294
N2A	16741	50446;50447;50448	chr2:178594569;178594568;178594567	chr2:179459296;179459295;179459294
N2B	10244	30955;30956;30957	chr2:178594569;178594568;178594567	chr2:179459296;179459295;179459294
Novex-1	10369	31330;31331;31332	chr2:178594569;178594568;178594567	chr2:179459296;179459295;179459294
Novex-2	10436	31531;31532;31533	chr2:178594569;178594568;178594567	chr2:179459296;179459295;179459294
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-28
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.6885
• Predicted PPI site: I

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/M	None	None	0.997	N	0.651	0.418	0.39619538035	gnomAD-4.0.0	6.8451E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99755E-07	0	0
K/R	None	None	0.998	N	0.607	0.238	0.427829143865	gnomAD-4.0.0	2.05353E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79951E-06	1.16093E-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
K/A	0.6451	likely_pathogenic	0.5783	pathogenic	0.039	Stabilizing	0.996	D	0.608	neutral	None	None	None	None	I
K/C	0.8983	likely_pathogenic	0.8741	pathogenic	-0.297	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
K/D	0.8973	likely_pathogenic	0.8436	pathogenic	-0.09	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
K/E	0.56	ambiguous	0.4546	ambiguous	-0.062	Destabilizing	0.998	D	0.631	neutral	N	0.467263335	None	None	I
K/F	0.9559	likely_pathogenic	0.9283	pathogenic	-0.015	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
K/G	0.8286	likely_pathogenic	0.7732	pathogenic	-0.19	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	I
K/H	0.638	likely_pathogenic	0.5868	pathogenic	-0.355	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
K/I	0.606	likely_pathogenic	0.5164	ambiguous	0.571	Stabilizing	0.995	D	0.649	neutral	None	None	None	None	I
K/L	0.6224	likely_pathogenic	0.5628	ambiguous	0.571	Stabilizing	0.269	N	0.361	neutral	None	None	None	None	I
K/M	0.5994	likely_pathogenic	0.5146	ambiguous	0.149	Stabilizing	0.997	D	0.651	neutral	N	0.519868455	None	None	I
K/N	0.8209	likely_pathogenic	0.7371	pathogenic	0.058	Stabilizing	0.999	D	0.683	prob.neutral	N	0.494220649	None	None	I
K/P	0.8685	likely_pathogenic	0.8413	pathogenic	0.422	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	I
K/Q	0.341	ambiguous	0.2941	benign	-0.062	Destabilizing	0.999	D	0.686	prob.neutral	N	0.467876519	None	None	I
K/R	0.1072	likely_benign	0.1061	benign	-0.127	Destabilizing	0.998	D	0.607	neutral	N	0.49523937	None	None	I
K/S	0.7988	likely_pathogenic	0.7173	pathogenic	-0.371	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
K/T	0.4968	ambiguous	0.4075	ambiguous	-0.192	Destabilizing	0.998	D	0.56	neutral	N	0.489948193	None	None	I
K/V	0.5375	ambiguous	0.477	ambiguous	0.422	Stabilizing	0.983	D	0.523	neutral	None	None	None	None	I
K/W	0.9568	likely_pathogenic	0.9319	pathogenic	-0.048	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
K/Y	0.9079	likely_pathogenic	0.8694	pathogenic	0.278	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	I

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.