TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28239	84940;84941;84942	chr2:178561417;178561416;178561415	chr2:179426144;179426143;179426142
N2AB	26598	80017;80018;80019	chr2:178561417;178561416;178561415	chr2:179426144;179426143;179426142
N2A	25671	77236;77237;77238	chr2:178561417;178561416;178561415	chr2:179426144;179426143;179426142
N2B	19174	57745;57746;57747	chr2:178561417;178561416;178561415	chr2:179426144;179426143;179426142
Novex-1	19299	58120;58121;58122	chr2:178561417;178561416;178561415	chr2:179426144;179426143;179426142
Novex-2	19366	58321;58322;58323	chr2:178561417;178561416;178561415	chr2:179426144;179426143;179426142
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-93
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.802
• Predicted PPI site: I

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
K/I	None	None	0.939	N	0.547	0.354	0.489449420884	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79892E-06	0	0
K/R	None	None	0.684	N	0.581	0.132	0.28798054836	gnomAD-4.0.0	6.84211E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9946E-07	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
K/A	0.556	ambiguous	0.4665	ambiguous	0.033	Stabilizing	0.543	D	0.497	neutral	None	None	None	None	I
K/C	0.8185	likely_pathogenic	0.7752	pathogenic	-0.267	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	I
K/D	0.7942	likely_pathogenic	0.7537	pathogenic	-0.177	Destabilizing	0.59	D	0.537	neutral	None	None	None	None	I
K/E	0.4565	ambiguous	0.3722	ambiguous	-0.188	Destabilizing	0.007	N	0.18	neutral	N	0.44144217	None	None	I
K/F	0.9044	likely_pathogenic	0.8781	pathogenic	-0.263	Destabilizing	0.984	D	0.543	neutral	None	None	None	None	I
K/G	0.6928	likely_pathogenic	0.6314	pathogenic	-0.122	Destabilizing	0.742	D	0.56	neutral	None	None	None	None	I
K/H	0.4992	ambiguous	0.4496	ambiguous	-0.305	Destabilizing	0.953	D	0.547	neutral	None	None	None	None	I
K/I	0.5887	likely_pathogenic	0.5113	ambiguous	0.359	Stabilizing	0.939	D	0.547	neutral	N	0.480865439	None	None	I
K/L	0.5885	likely_pathogenic	0.5149	ambiguous	0.359	Stabilizing	0.742	D	0.562	neutral	None	None	None	None	I
K/M	0.5055	ambiguous	0.4366	ambiguous	0.1	Stabilizing	0.996	D	0.547	neutral	None	None	None	None	I
K/N	0.6799	likely_pathogenic	0.6179	pathogenic	0.181	Stabilizing	0.684	D	0.541	neutral	N	0.472116027	None	None	I
K/P	0.5408	ambiguous	0.4662	ambiguous	0.276	Stabilizing	0.004	N	0.207	neutral	None	None	None	None	I
K/Q	0.2636	likely_benign	0.214	benign	None	Stabilizing	0.521	D	0.61	neutral	N	0.500663832	None	None	I
K/R	0.1012	likely_benign	0.0913	benign	-0.019	Destabilizing	0.684	D	0.581	neutral	N	0.496892808	None	None	I
K/S	0.6637	likely_pathogenic	0.5984	pathogenic	-0.228	Destabilizing	0.742	D	0.503	neutral	None	None	None	None	I
K/T	0.4319	ambiguous	0.3589	ambiguous	-0.111	Destabilizing	0.684	D	0.565	neutral	N	0.471862537	None	None	I
K/V	0.5559	ambiguous	0.4746	ambiguous	0.276	Stabilizing	0.854	D	0.553	neutral	None	None	None	None	I
K/W	0.9056	likely_pathogenic	0.8906	pathogenic	-0.324	Destabilizing	0.996	D	0.676	prob.neutral	None	None	None	None	I
K/Y	0.7948	likely_pathogenic	0.7605	pathogenic	0.033	Stabilizing	0.984	D	0.555	neutral	None	None	None	None	I

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.