TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31053	93382;93383;93384	chr2:178548469;178548468;178548467	chr2:179413196;179413195;179413194
N2AB	29412	88459;88460;88461	chr2:178548469;178548468;178548467	chr2:179413196;179413195;179413194
N2A	28485	85678;85679;85680	chr2:178548469;178548468;178548467	chr2:179413196;179413195;179413194
N2B	21988	66187;66188;66189	chr2:178548469;178548468;178548467	chr2:179413196;179413195;179413194
Novex-1	22113	66562;66563;66564	chr2:178548469;178548468;178548467	chr2:179413196;179413195;179413194
Novex-2	22180	66763;66764;66765	chr2:178548469;178548468;178548467	chr2:179413196;179413195;179413194
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-114
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0849
• 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
V/A	None	None	0.334	D	0.605	0.534	0.671746105685	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
V/L	None	None	0.002	N	0.333	0.142	0.348764635752	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
V/A	0.6304	likely_pathogenic	0.585	pathogenic	-2.284	Highly Destabilizing	0.334	N	0.605	neutral	D	0.548389794	None	None	N
V/C	0.9403	likely_pathogenic	0.9339	pathogenic	-1.829	Destabilizing	0.982	D	0.762	deleterious	None	None	None	None	N
V/D	0.9964	likely_pathogenic	0.9951	pathogenic	-3.275	Highly Destabilizing	0.826	D	0.903	deleterious	None	None	None	None	N
V/E	0.988	likely_pathogenic	0.984	pathogenic	-2.953	Highly Destabilizing	0.781	D	0.877	deleterious	D	0.567254517	None	None	N
V/F	0.6706	likely_pathogenic	0.6791	pathogenic	-1.311	Destabilizing	0.7	D	0.769	deleterious	None	None	None	None	N
V/G	0.8926	likely_pathogenic	0.8679	pathogenic	-2.91	Highly Destabilizing	0.781	D	0.896	deleterious	D	0.567254517	None	None	N
V/H	0.9956	likely_pathogenic	0.9943	pathogenic	-2.867	Highly Destabilizing	0.982	D	0.873	deleterious	None	None	None	None	N
V/I	0.0708	likely_benign	0.0727	benign	-0.47	Destabilizing	0.002	N	0.273	neutral	N	0.463151168	None	None	N
V/K	0.9912	likely_pathogenic	0.9887	pathogenic	-1.899	Destabilizing	0.826	D	0.877	deleterious	None	None	None	None	N
V/L	0.2608	likely_benign	0.2287	benign	-0.47	Destabilizing	0.002	N	0.333	neutral	N	0.521183538	None	None	N
V/M	0.3577	ambiguous	0.3544	ambiguous	-0.749	Destabilizing	0.7	D	0.663	neutral	None	None	None	None	N
V/N	0.987	likely_pathogenic	0.9841	pathogenic	-2.578	Highly Destabilizing	0.935	D	0.913	deleterious	None	None	None	None	N
V/P	0.9821	likely_pathogenic	0.9715	pathogenic	-1.054	Destabilizing	0.935	D	0.89	deleterious	None	None	None	None	N
V/Q	0.9851	likely_pathogenic	0.9805	pathogenic	-2.214	Highly Destabilizing	0.935	D	0.902	deleterious	None	None	None	None	N
V/R	0.9833	likely_pathogenic	0.9784	pathogenic	-2.006	Highly Destabilizing	0.826	D	0.913	deleterious	None	None	None	None	N
V/S	0.9337	likely_pathogenic	0.9206	pathogenic	-3.116	Highly Destabilizing	0.826	D	0.859	deleterious	None	None	None	None	N
V/T	0.7109	likely_pathogenic	0.6816	pathogenic	-2.627	Highly Destabilizing	0.399	N	0.631	neutral	None	None	None	None	N
V/W	0.9908	likely_pathogenic	0.9899	pathogenic	-1.922	Destabilizing	0.982	D	0.846	deleterious	None	None	None	None	N
V/Y	0.9749	likely_pathogenic	0.9714	pathogenic	-1.552	Destabilizing	0.826	D	0.771	deleterious	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.