TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33287	100084;100085;100086	chr2:178537348;178537347;178537346	chr2:179402075;179402074;179402073
N2AB	31646	95161;95162;95163	chr2:178537348;178537347;178537346	chr2:179402075;179402074;179402073
N2A	30719	92380;92381;92382	chr2:178537348;178537347;178537346	chr2:179402075;179402074;179402073
N2B	24222	72889;72890;72891	chr2:178537348;178537347;178537346	chr2:179402075;179402074;179402073
Novex-1	24347	73264;73265;73266	chr2:178537348;178537347;178537346	chr2:179402075;179402074;179402073
Novex-2	24414	73465;73466;73467	chr2:178537348;178537347;178537346	chr2:179402075;179402074;179402073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-157
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.1184
• 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
I/M	rs758948672	-1.69	0.369	N	0.665	0.461	0.580477355671	gnomAD-2.1.1	1.54E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.21E-05	0
I/M	rs758948672	-1.69	0.369	N	0.665	0.461	0.580477355671	gnomAD-4.0.0	5.36517E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.41212E-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
I/A	0.9854	likely_pathogenic	0.9892	pathogenic	-2.597	Highly Destabilizing	0.851	D	0.579	neutral	None	None	None	None	N
I/C	0.9827	likely_pathogenic	0.9887	pathogenic	-1.849	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	N
I/D	0.9992	likely_pathogenic	0.9993	pathogenic	-2.682	Highly Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
I/E	0.9976	likely_pathogenic	0.9981	pathogenic	-2.55	Highly Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
I/F	0.6868	likely_pathogenic	0.7423	pathogenic	-1.562	Destabilizing	0.976	D	0.658	neutral	None	None	None	None	N
I/G	0.9975	likely_pathogenic	0.9982	pathogenic	-3.044	Highly Destabilizing	0.988	D	0.675	neutral	None	None	None	None	N
I/H	0.9972	likely_pathogenic	0.9981	pathogenic	-2.214	Highly Destabilizing	0.997	D	0.669	neutral	None	None	None	None	N
I/K	0.9955	likely_pathogenic	0.9966	pathogenic	-1.941	Destabilizing	0.982	D	0.686	prob.neutral	N	0.499555347	None	None	N
I/L	0.4728	ambiguous	0.5004	ambiguous	-1.341	Destabilizing	0.004	N	0.606	neutral	N	0.496259983	None	None	N
I/M	0.46	ambiguous	0.522	ambiguous	-1.276	Destabilizing	0.369	N	0.665	neutral	N	0.499048368	None	None	N
I/N	0.9811	likely_pathogenic	0.9842	pathogenic	-2.026	Highly Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
I/P	0.9951	likely_pathogenic	0.9959	pathogenic	-1.738	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
I/Q	0.9961	likely_pathogenic	0.9972	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
I/R	0.9939	likely_pathogenic	0.9955	pathogenic	-1.406	Destabilizing	0.999	D	0.688	prob.neutral	N	0.499555347	None	None	N
I/S	0.9868	likely_pathogenic	0.9899	pathogenic	-2.7	Highly Destabilizing	0.976	D	0.629	neutral	None	None	None	None	N
I/T	0.9765	likely_pathogenic	0.9842	pathogenic	-2.449	Highly Destabilizing	0.721	D	0.645	neutral	N	0.499048368	None	None	N
I/V	0.2285	likely_benign	0.2667	benign	-1.738	Destabilizing	None	N	0.412	neutral	N	0.474594739	None	None	N
I/W	0.9939	likely_pathogenic	0.9954	pathogenic	-1.783	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
I/Y	0.9696	likely_pathogenic	0.9764	pathogenic	-1.592	Destabilizing	0.791	D	0.645	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.