TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6462	19609;19610;19611	chr2:178728542;178728541;178728540	chr2:179593269;179593268;179593267
N2AB	6145	18658;18659;18660	chr2:178728542;178728541;178728540	chr2:179593269;179593268;179593267
N2A	5218	15877;15878;15879	chr2:178728542;178728541;178728540	chr2:179593269;179593268;179593267
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-48
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.5911
• 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
D/A	rs1419616263	-0.114	0.896	N	0.405	0.336	0.416581338634	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66889E-04
D/A	rs1419616263	-0.114	0.896	N	0.405	0.336	0.416581338634	gnomAD-4.0.0	2.05436E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00015E-07	1.1609E-05	1.6581E-05

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
D/A	0.1375	likely_benign	0.1506	benign	-0.198	Destabilizing	0.896	D	0.405	neutral	N	0.519223455	None	None	I
D/C	0.6857	likely_pathogenic	0.7226	pathogenic	-0.038	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
D/E	0.1365	likely_benign	0.1475	benign	-0.222	Destabilizing	0.026	N	0.251	neutral	N	0.470274715	None	None	I
D/F	0.6437	likely_pathogenic	0.6651	pathogenic	-0.086	Destabilizing	0.988	D	0.537	neutral	None	None	None	None	I
D/G	0.204	likely_benign	0.206	benign	-0.383	Destabilizing	0.896	D	0.351	neutral	N	0.499984334	None	None	I
D/H	0.2958	likely_benign	0.3104	benign	0.216	Stabilizing	0.026	N	0.249	neutral	N	0.496194667	None	None	I
D/I	0.2761	likely_benign	0.3001	benign	0.238	Stabilizing	0.988	D	0.527	neutral	None	None	None	None	I
D/K	0.3074	likely_benign	0.3315	benign	0.376	Stabilizing	0.851	D	0.375	neutral	None	None	None	None	I
D/L	0.3607	ambiguous	0.4065	ambiguous	0.238	Stabilizing	0.976	D	0.486	neutral	None	None	None	None	I
D/M	0.5763	likely_pathogenic	0.607	pathogenic	0.243	Stabilizing	0.999	D	0.554	neutral	None	None	None	None	I
D/N	0.1023	likely_benign	0.1101	benign	0.036	Stabilizing	0.896	D	0.353	neutral	D	0.528805731	None	None	I
D/P	0.6212	likely_pathogenic	0.661	pathogenic	0.114	Stabilizing	0.988	D	0.358	neutral	None	None	None	None	I
D/Q	0.3051	likely_benign	0.3312	benign	0.084	Stabilizing	0.952	D	0.286	neutral	None	None	None	None	I
D/R	0.3347	likely_benign	0.3405	ambiguous	0.585	Stabilizing	0.976	D	0.428	neutral	None	None	None	None	I
D/S	0.1203	likely_benign	0.1301	benign	-0.063	Destabilizing	0.919	D	0.309	neutral	None	None	None	None	I
D/T	0.2062	likely_benign	0.2339	benign	0.09	Stabilizing	0.919	D	0.347	neutral	None	None	None	None	I
D/V	0.172	likely_benign	0.1856	benign	0.114	Stabilizing	0.984	D	0.489	neutral	D	0.533635547	None	None	I
D/W	0.9176	likely_pathogenic	0.9165	pathogenic	0.049	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	I
D/Y	0.2593	likely_benign	0.257	benign	0.158	Stabilizing	0.968	D	0.531	neutral	N	0.482756722	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.