TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23129	69610;69611;69612	chr2:178576950;178576949;178576948	chr2:179441677;179441676;179441675
N2AB	21488	64687;64688;64689	chr2:178576950;178576949;178576948	chr2:179441677;179441676;179441675
N2A	20561	61906;61907;61908	chr2:178576950;178576949;178576948	chr2:179441677;179441676;179441675
N2B	14064	42415;42416;42417	chr2:178576950;178576949;178576948	chr2:179441677;179441676;179441675
Novex-1	14189	42790;42791;42792	chr2:178576950;178576949;178576948	chr2:179441677;179441676;179441675
Novex-2	14256	42991;42992;42993	chr2:178576950;178576949;178576948	chr2:179441677;179441676;179441675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-55
• Domain position: 90
• Structural Position: 125
• Q(SASA): 0.8682
• 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
E/G	rs755308234	0.006	None	N	0.222	0.168	0.310458034454	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/G	rs755308234	0.006	None	N	0.222	0.168	0.310458034454	gnomAD-4.0.0	1.36883E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79941E-05	0	0
E/K	rs1394354671	0.666	0.181	N	0.387	0.274	0.290590437066	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1394354671	0.666	0.181	N	0.387	0.274	0.290590437066	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43386E-05	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
E/A	0.1079	likely_benign	0.1009	benign	-0.135	Destabilizing	0.001	N	0.287	neutral	D	0.529248448	None	None	N
E/C	0.7055	likely_pathogenic	0.6419	pathogenic	-0.274	Destabilizing	0.887	D	0.373	neutral	None	None	None	None	N
E/D	0.0796	likely_benign	0.0724	benign	-0.307	Destabilizing	0.001	N	0.183	neutral	N	0.482160838	None	None	N
E/F	0.6294	likely_pathogenic	0.5576	ambiguous	0.008	Stabilizing	0.676	D	0.391	neutral	None	None	None	None	N
E/G	0.1123	likely_benign	0.1113	benign	-0.293	Destabilizing	None	N	0.222	neutral	N	0.487947736	None	None	N
E/H	0.3584	ambiguous	0.3137	benign	0.595	Stabilizing	0.864	D	0.365	neutral	None	None	None	None	N
E/I	0.2365	likely_benign	0.2056	benign	0.235	Stabilizing	0.507	D	0.451	neutral	None	None	None	None	N
E/K	0.1016	likely_benign	0.0972	benign	0.378	Stabilizing	0.181	N	0.387	neutral	N	0.499313587	None	None	N
E/L	0.2472	likely_benign	0.2134	benign	0.235	Stabilizing	0.128	N	0.448	neutral	None	None	None	None	N
E/M	0.3221	likely_benign	0.2702	benign	0.018	Stabilizing	0.887	D	0.399	neutral	None	None	None	None	N
E/N	0.1668	likely_benign	0.1484	benign	-0.037	Destabilizing	0.128	N	0.374	neutral	None	None	None	None	N
E/P	0.2593	likely_benign	0.2307	benign	0.13	Stabilizing	0.507	D	0.417	neutral	None	None	None	None	N
E/Q	0.1106	likely_benign	0.1031	benign	0.012	Stabilizing	0.31	N	0.46	neutral	N	0.4949984	None	None	N
E/R	0.1995	likely_benign	0.1849	benign	0.691	Stabilizing	0.507	D	0.357	neutral	None	None	None	None	N
E/S	0.1304	likely_benign	0.1184	benign	-0.163	Destabilizing	0.057	N	0.325	neutral	None	None	None	None	N
E/T	0.1573	likely_benign	0.1406	benign	-0.02	Destabilizing	0.128	N	0.348	neutral	None	None	None	None	N
E/V	0.1501	likely_benign	0.1323	benign	0.13	Stabilizing	0.1	N	0.41	neutral	N	0.515331154	None	None	N
E/W	0.8372	likely_pathogenic	0.7768	pathogenic	0.125	Stabilizing	0.96	D	0.449	neutral	None	None	None	None	N
E/Y	0.49	ambiguous	0.4167	ambiguous	0.246	Stabilizing	0.864	D	0.418	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.