TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28603	86032;86033;86034	chr2:178560325;178560324;178560323	chr2:179425052;179425051;179425050
N2AB	26962	81109;81110;81111	chr2:178560325;178560324;178560323	chr2:179425052;179425051;179425050
N2A	26035	78328;78329;78330	chr2:178560325;178560324;178560323	chr2:179425052;179425051;179425050
N2B	19538	58837;58838;58839	chr2:178560325;178560324;178560323	chr2:179425052;179425051;179425050
Novex-1	19663	59212;59213;59214	chr2:178560325;178560324;178560323	chr2:179425052;179425051;179425050
Novex-2	19730	59413;59414;59415	chr2:178560325;178560324;178560323	chr2:179425052;179425051;179425050
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: Fn3-96
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.539
• 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	0.967	N	0.645	0.345	0.543209242439	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02425E-05
K/N	rs778444893	None	0.967	N	0.581	0.232	0.12205267543	gnomAD-4.0.0	6.84212E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.7343E-04	0	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	0.5526	ambiguous	0.4424	ambiguous	0.069	Stabilizing	0.845	D	0.505	neutral	None	None	None	None	I
K/C	0.7584	likely_pathogenic	0.7023	pathogenic	-0.333	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
K/D	0.7093	likely_pathogenic	0.6427	pathogenic	-0.263	Destabilizing	0.975	D	0.557	neutral	None	None	None	None	I
K/E	0.4126	ambiguous	0.312	benign	-0.26	Destabilizing	0.892	D	0.487	neutral	N	0.458547851	None	None	I
K/F	0.816	likely_pathogenic	0.7408	pathogenic	-0.228	Destabilizing	0.987	D	0.662	neutral	None	None	None	None	I
K/G	0.6282	likely_pathogenic	0.5574	ambiguous	-0.078	Destabilizing	0.975	D	0.516	neutral	None	None	None	None	I
K/H	0.3653	ambiguous	0.3096	benign	-0.189	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	I
K/I	0.4666	ambiguous	0.3604	ambiguous	0.378	Stabilizing	0.967	D	0.645	neutral	N	0.502570774	None	None	I
K/L	0.4667	ambiguous	0.3646	ambiguous	0.378	Stabilizing	0.845	D	0.491	neutral	None	None	None	None	I
K/M	0.3187	likely_benign	0.242	benign	-0.104	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	I
K/N	0.5229	ambiguous	0.4424	ambiguous	0.123	Stabilizing	0.967	D	0.581	neutral	N	0.495143369	None	None	I
K/P	0.8985	likely_pathogenic	0.858	pathogenic	0.299	Stabilizing	0.987	D	0.583	neutral	None	None	None	None	I
K/Q	0.2056	likely_benign	0.1641	benign	0.012	Stabilizing	0.983	D	0.602	neutral	N	0.469996995	None	None	I
K/R	0.0949	likely_benign	0.0886	benign	-0.015	Destabilizing	0.892	D	0.493	neutral	N	0.430497245	None	None	I
K/S	0.5897	likely_pathogenic	0.4955	ambiguous	-0.204	Destabilizing	0.845	D	0.481	neutral	None	None	None	None	I
K/T	0.2762	likely_benign	0.2046	benign	-0.08	Destabilizing	0.025	N	0.336	neutral	N	0.447408137	None	None	I
K/V	0.4411	ambiguous	0.3365	benign	0.299	Stabilizing	0.95	D	0.512	neutral	None	None	None	None	I
K/W	0.7987	likely_pathogenic	0.7458	pathogenic	-0.356	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
K/Y	0.6283	likely_pathogenic	0.5679	pathogenic	-0.002	Destabilizing	0.996	D	0.603	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.