TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23094	69505;69506;69507	chr2:178577055;178577054;178577053	chr2:179441782;179441781;179441780
N2AB	21453	64582;64583;64584	chr2:178577055;178577054;178577053	chr2:179441782;179441781;179441780
N2A	20526	61801;61802;61803	chr2:178577055;178577054;178577053	chr2:179441782;179441781;179441780
N2B	14029	42310;42311;42312	chr2:178577055;178577054;178577053	chr2:179441782;179441781;179441780
Novex-1	14154	42685;42686;42687	chr2:178577055;178577054;178577053	chr2:179441782;179441781;179441780
Novex-2	14221	42886;42887;42888	chr2:178577055;178577054;178577053	chr2:179441782;179441781;179441780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-55
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.0877
• 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/T	rs1462335969	None	0.684	N	0.559	0.289	0.578198000816	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	6.56E-05	0	0	0	None	0	0	0	0	0
I/T	rs1462335969	None	0.684	N	0.559	0.289	0.578198000816	gnomAD-4.0.0	4.95875E-06	None	None	None	None	N	None	2.67144E-05	3.33522E-05	None	0	0	None	0	0	3.39105E-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	0.6207	likely_pathogenic	0.5888	pathogenic	-2.419	Highly Destabilizing	0.004	N	0.329	neutral	None	None	None	None	N
I/C	0.7196	likely_pathogenic	0.6882	pathogenic	-1.802	Destabilizing	0.987	D	0.543	neutral	None	None	None	None	N
I/D	0.935	likely_pathogenic	0.9175	pathogenic	-2.161	Highly Destabilizing	0.953	D	0.619	neutral	None	None	None	None	N
I/E	0.9015	likely_pathogenic	0.879	pathogenic	-1.997	Destabilizing	0.91	D	0.636	neutral	None	None	None	None	N
I/F	0.4198	ambiguous	0.3961	ambiguous	-1.51	Destabilizing	0.939	D	0.631	neutral	N	0.471595821	None	None	N
I/G	0.872	likely_pathogenic	0.8537	pathogenic	-2.922	Highly Destabilizing	0.59	D	0.635	neutral	None	None	None	None	N
I/H	0.8651	likely_pathogenic	0.8393	pathogenic	-2.231	Highly Destabilizing	0.996	D	0.589	neutral	None	None	None	None	N
I/K	0.8636	likely_pathogenic	0.8305	pathogenic	-1.661	Destabilizing	0.91	D	0.635	neutral	None	None	None	None	N
I/L	0.1247	likely_benign	0.1373	benign	-1.0	Destabilizing	0.164	N	0.423	neutral	N	0.473861233	None	None	N
I/M	0.1774	likely_benign	0.169	benign	-0.961	Destabilizing	0.939	D	0.62	neutral	N	0.500933191	None	None	N
I/N	0.6161	likely_pathogenic	0.5314	ambiguous	-1.789	Destabilizing	0.939	D	0.634	neutral	N	0.462717823	None	None	N
I/P	0.8972	likely_pathogenic	0.9015	pathogenic	-1.45	Destabilizing	0.953	D	0.627	neutral	None	None	None	None	N
I/Q	0.8205	likely_pathogenic	0.7927	pathogenic	-1.756	Destabilizing	0.953	D	0.637	neutral	None	None	None	None	N
I/R	0.8212	likely_pathogenic	0.7848	pathogenic	-1.306	Destabilizing	0.953	D	0.633	neutral	None	None	None	None	N
I/S	0.5924	likely_pathogenic	0.5293	ambiguous	-2.579	Highly Destabilizing	0.521	D	0.605	neutral	N	0.515822499	None	None	N
I/T	0.5245	ambiguous	0.4782	ambiguous	-2.268	Highly Destabilizing	0.684	D	0.559	neutral	N	0.519268236	None	None	N
I/V	0.1012	likely_benign	0.0995	benign	-1.45	Destabilizing	0.004	N	0.164	neutral	N	0.39849947	None	None	N
I/W	0.9507	likely_pathogenic	0.9497	pathogenic	-1.748	Destabilizing	0.996	D	0.638	neutral	None	None	None	None	N
I/Y	0.8512	likely_pathogenic	0.8195	pathogenic	-1.496	Destabilizing	0.984	D	0.616	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.