TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10097	30514;30515;30516	chr2:178702598;178702597;178702596	chr2:179567325;179567324;179567323
N2AB	9780	29563;29564;29565	chr2:178702598;178702597;178702596	chr2:179567325;179567324;179567323
N2A	8853	26782;26783;26784	chr2:178702598;178702597;178702596	chr2:179567325;179567324;179567323
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-86
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0633
• 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
F/S	None	None	0.999	None	0.867	0.878	0.869272637459	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
F/A	0.9995	likely_pathogenic	0.9995	pathogenic	-2.045	Highly Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	N
F/C	0.9994	likely_pathogenic	0.9993	pathogenic	-1.108	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
F/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.053	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
F/E	0.9999	likely_pathogenic	0.9999	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
F/G	0.9998	likely_pathogenic	0.9997	pathogenic	-2.518	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
F/H	0.9996	likely_pathogenic	0.9996	pathogenic	-1.778	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
F/I	0.9912	likely_pathogenic	0.992	pathogenic	-0.49	Destabilizing	0.978	D	0.62	neutral	None	None	None	None	N
F/K	0.9999	likely_pathogenic	0.9999	pathogenic	-1.635	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
F/L	0.9981	likely_pathogenic	0.9972	pathogenic	-0.49	Destabilizing	0.217	N	0.289	neutral	None	None	None	None	N
F/M	0.9926	likely_pathogenic	0.9891	pathogenic	-0.386	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
F/N	0.9999	likely_pathogenic	0.9999	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-1.022	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
F/Q	0.9998	likely_pathogenic	0.9998	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
F/R	0.9995	likely_pathogenic	0.9995	pathogenic	-1.723	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
F/S	0.9998	likely_pathogenic	0.9998	pathogenic	-2.765	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
F/T	0.9997	likely_pathogenic	0.9997	pathogenic	-2.376	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
F/V	0.9928	likely_pathogenic	0.9927	pathogenic	-1.022	Destabilizing	0.978	D	0.694	prob.neutral	None	None	None	None	N
F/W	0.9885	likely_pathogenic	0.9871	pathogenic	0.047	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	N
F/Y	0.9674	likely_pathogenic	0.9618	pathogenic	-0.32	Destabilizing	0.998	D	0.581	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.