TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31578	94957;94958;94959	chr2:178546696;178546695;178546694	chr2:179411423;179411422;179411421
N2AB	29937	90034;90035;90036	chr2:178546696;178546695;178546694	chr2:179411423;179411422;179411421
N2A	29010	87253;87254;87255	chr2:178546696;178546695;178546694	chr2:179411423;179411422;179411421
N2B	22513	67762;67763;67764	chr2:178546696;178546695;178546694	chr2:179411423;179411422;179411421
Novex-1	22638	68137;68138;68139	chr2:178546696;178546695;178546694	chr2:179411423;179411422;179411421
Novex-2	22705	68338;68339;68340	chr2:178546696;178546695;178546694	chr2:179411423;179411422;179411421
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-118
• Domain position: 73
• Structural Position: 102
• Q(SASA): 0.1137
• 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
D/E	rs2154146101	None	0.004	N	0.093	0.131	0.0846915920261	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	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
D/A	0.2002	likely_benign	0.2104	benign	-0.609	Destabilizing	0.896	D	0.514	neutral	N	0.375025177	None	None	N
D/C	0.694	likely_pathogenic	0.6828	pathogenic	-0.076	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
D/E	0.1592	likely_benign	0.145	benign	-0.534	Destabilizing	0.004	N	0.093	neutral	N	0.366752411	None	None	N
D/F	0.7175	likely_pathogenic	0.7022	pathogenic	-0.444	Destabilizing	0.996	D	0.666	neutral	None	None	None	None	N
D/G	0.2465	likely_benign	0.2604	benign	-0.875	Destabilizing	0.896	D	0.491	neutral	N	0.386994397	None	None	N
D/H	0.4096	ambiguous	0.4143	ambiguous	-0.582	Destabilizing	0.984	D	0.547	neutral	N	0.393824369	None	None	N
D/I	0.5543	ambiguous	0.5142	ambiguous	0.068	Stabilizing	0.988	D	0.648	neutral	None	None	None	None	N
D/K	0.5227	ambiguous	0.509	ambiguous	-0.038	Destabilizing	0.851	D	0.476	neutral	None	None	None	None	N
D/L	0.5277	ambiguous	0.5315	ambiguous	0.068	Stabilizing	0.976	D	0.597	neutral	None	None	None	None	N
D/M	0.6568	likely_pathogenic	0.6252	pathogenic	0.485	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
D/N	0.1243	likely_benign	0.1237	benign	-0.426	Destabilizing	0.896	D	0.504	neutral	N	0.395363164	None	None	N
D/P	0.9739	likely_pathogenic	0.9686	pathogenic	-0.135	Destabilizing	0.988	D	0.516	neutral	None	None	None	None	N
D/Q	0.3376	likely_benign	0.3357	benign	-0.352	Destabilizing	0.851	D	0.509	neutral	None	None	None	None	N
D/R	0.5869	likely_pathogenic	0.584	pathogenic	0.091	Stabilizing	0.976	D	0.548	neutral	None	None	None	None	N
D/S	0.1446	likely_benign	0.1454	benign	-0.579	Destabilizing	0.919	D	0.465	neutral	None	None	None	None	N
D/T	0.3534	ambiguous	0.3286	benign	-0.362	Destabilizing	0.919	D	0.522	neutral	None	None	None	None	N
D/V	0.3574	ambiguous	0.3406	ambiguous	-0.135	Destabilizing	0.984	D	0.597	neutral	N	0.384876811	None	None	N
D/W	0.9484	likely_pathogenic	0.9422	pathogenic	-0.255	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
D/Y	0.3732	ambiguous	0.3672	ambiguous	-0.202	Destabilizing	0.995	D	0.665	neutral	N	0.502453344	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.