TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14371	43336;43337;43338	chr2:178633020;178633019;178633018	chr2:179497747;179497746;179497745
N2AB	12730	38413;38414;38415	chr2:178633020;178633019;178633018	chr2:179497747;179497746;179497745
N2A	11803	35632;35633;35634	chr2:178633020;178633019;178633018	chr2:179497747;179497746;179497745
N2B	5306	16141;16142;16143	chr2:178633020;178633019;178633018	chr2:179497747;179497746;179497745
Novex-1	5431	16516;16517;16518	chr2:178633020;178633019;178633018	chr2:179497747;179497746;179497745
Novex-2	5498	16717;16718;16719	chr2:178633020;178633019;178633018	chr2:179497747;179497746;179497745
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-94
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.1943
• 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/M	rs757765087	0.152	0.8	N	0.404	0.211	0.243972157842	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
K/M	rs757765087	0.152	0.8	N	0.404	0.211	0.243972157842	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43349E-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
K/A	0.786	likely_pathogenic	0.6702	pathogenic	-0.604	Destabilizing	0.004	N	0.154	neutral	None	None	None	None	N
K/C	0.8905	likely_pathogenic	0.8428	pathogenic	-0.61	Destabilizing	0.984	D	0.429	neutral	None	None	None	None	N
K/D	0.8907	likely_pathogenic	0.7811	pathogenic	-0.44	Destabilizing	0.428	N	0.448	neutral	None	None	None	None	N
K/E	0.5203	ambiguous	0.3977	ambiguous	-0.323	Destabilizing	0.104	N	0.403	neutral	D	0.527160786	None	None	N
K/F	0.9639	likely_pathogenic	0.9352	pathogenic	-0.225	Destabilizing	0.942	D	0.451	neutral	None	None	None	None	N
K/G	0.7712	likely_pathogenic	0.6335	pathogenic	-0.989	Destabilizing	0.272	N	0.411	neutral	None	None	None	None	N
K/H	0.6608	likely_pathogenic	0.5569	ambiguous	-1.372	Destabilizing	0.842	D	0.405	neutral	None	None	None	None	N
K/I	0.8522	likely_pathogenic	0.7834	pathogenic	0.403	Stabilizing	0.842	D	0.479	neutral	None	None	None	None	N
K/L	0.7234	likely_pathogenic	0.6609	pathogenic	0.403	Stabilizing	0.428	N	0.444	neutral	None	None	None	None	N
K/M	0.5756	likely_pathogenic	0.4955	ambiguous	0.356	Stabilizing	0.8	D	0.404	neutral	N	0.469187063	None	None	N
K/N	0.6921	likely_pathogenic	0.5617	ambiguous	-0.674	Destabilizing	0.361	N	0.405	neutral	N	0.416850722	None	None	N
K/P	0.9101	likely_pathogenic	0.8328	pathogenic	0.098	Stabilizing	0.002	N	0.269	neutral	None	None	None	None	N
K/Q	0.31	likely_benign	0.2478	benign	-0.74	Destabilizing	0.008	N	0.213	neutral	N	0.465876024	None	None	N
K/R	0.1045	likely_benign	0.1002	benign	-0.802	Destabilizing	0.22	N	0.423	neutral	N	0.436892645	None	None	N
K/S	0.7774	likely_pathogenic	0.6529	pathogenic	-1.281	Destabilizing	0.134	N	0.329	neutral	None	None	None	None	N
K/T	0.5575	ambiguous	0.4533	ambiguous	-0.958	Destabilizing	0.361	N	0.423	neutral	N	0.432506033	None	None	N
K/V	0.8119	likely_pathogenic	0.7473	pathogenic	0.098	Stabilizing	0.428	N	0.415	neutral	None	None	None	None	N
K/W	0.9451	likely_pathogenic	0.9105	pathogenic	-0.128	Destabilizing	0.984	D	0.551	neutral	None	None	None	None	N
K/Y	0.9068	likely_pathogenic	0.8367	pathogenic	0.163	Stabilizing	0.842	D	0.469	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.