TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5855	17788;17789;17790	chr2:178731102;178731101;178731100	chr2:179595829;179595828;179595827
N2AB	5538	16837;16838;16839	chr2:178731102;178731101;178731100	chr2:179595829;179595828;179595827
N2A	4611	14056;14057;14058	chr2:178731102;178731101;178731100	chr2:179595829;179595828;179595827
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-42
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2934
• 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
K/E	None	None	0.027	N	0.551	0.205	0.282179105231	gnomAD-4.0.0	2.05271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69853E-06	0	0
K/R	rs772017452	-0.636	None	N	0.208	0.111	0.236278675362	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/R	rs772017452	-0.636	None	N	0.208	0.111	0.236278675362	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
K/R	rs772017452	-0.636	None	N	0.208	0.111	0.236278675362	gnomAD-4.0.0	2.56249E-06	None	None	None	None	N	None	0	0	None	0	2.42495E-05	None	0	0	2.39329E-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
K/A	0.3505	ambiguous	0.4167	ambiguous	-0.919	Destabilizing	0.067	N	0.513	neutral	None	None	None	None	N
K/C	0.587	likely_pathogenic	0.6848	pathogenic	-0.882	Destabilizing	0.935	D	0.599	neutral	None	None	None	None	N
K/D	0.706	likely_pathogenic	0.7908	pathogenic	-0.776	Destabilizing	0.149	N	0.55	neutral	None	None	None	None	N
K/E	0.2155	likely_benign	0.2793	benign	-0.553	Destabilizing	0.027	N	0.551	neutral	N	0.51870338	None	None	N
K/F	0.756	likely_pathogenic	0.8349	pathogenic	-0.194	Destabilizing	0.38	N	0.601	neutral	None	None	None	None	N
K/G	0.4299	ambiguous	0.5504	ambiguous	-1.365	Destabilizing	0.149	N	0.56	neutral	None	None	None	None	N
K/H	0.2678	likely_benign	0.3084	benign	-1.318	Destabilizing	0.555	D	0.595	neutral	None	None	None	None	N
K/I	0.3739	ambiguous	0.4592	ambiguous	0.305	Stabilizing	0.188	N	0.605	neutral	D	0.526229572	None	None	N
K/L	0.3719	ambiguous	0.4476	ambiguous	0.305	Stabilizing	0.035	N	0.533	neutral	None	None	None	None	N
K/M	0.2595	likely_benign	0.3123	benign	-0.049	Destabilizing	0.016	N	0.393	neutral	None	None	None	None	N
K/N	0.4287	ambiguous	0.524	ambiguous	-1.091	Destabilizing	0.117	N	0.522	neutral	N	0.486226215	None	None	N
K/P	0.9583	likely_pathogenic	0.9754	pathogenic	-0.077	Destabilizing	0.555	D	0.601	neutral	None	None	None	None	N
K/Q	0.1282	likely_benign	0.1477	benign	-0.911	Destabilizing	0.002	N	0.378	neutral	N	0.500600409	None	None	N
K/R	0.0694	likely_benign	0.0765	benign	-0.651	Destabilizing	None	N	0.208	neutral	N	0.493135719	None	None	N
K/S	0.3673	ambiguous	0.4477	ambiguous	-1.68	Destabilizing	0.035	N	0.509	neutral	None	None	None	None	N
K/T	0.1719	likely_benign	0.2039	benign	-1.221	Destabilizing	0.002	N	0.324	neutral	N	0.478184909	None	None	N
K/V	0.3204	likely_benign	0.3803	ambiguous	-0.077	Destabilizing	0.081	N	0.559	neutral	None	None	None	None	N
K/W	0.7126	likely_pathogenic	0.8076	pathogenic	-0.158	Destabilizing	0.935	D	0.619	neutral	None	None	None	None	N
K/Y	0.6171	likely_pathogenic	0.7145	pathogenic	0.137	Stabilizing	0.555	D	0.6	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.