TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17741	53446;53447;53448	chr2:178607467;178607466;178607465	chr2:179472194;179472193;179472192
N2AB	16100	48523;48524;48525	chr2:178607467;178607466;178607465	chr2:179472194;179472193;179472192
N2A	15173	45742;45743;45744	chr2:178607467;178607466;178607465	chr2:179472194;179472193;179472192
N2B	8676	26251;26252;26253	chr2:178607467;178607466;178607465	chr2:179472194;179472193;179472192
Novex-1	8801	26626;26627;26628	chr2:178607467;178607466;178607465	chr2:179472194;179472193;179472192
Novex-2	8868	26827;26828;26829	chr2:178607467;178607466;178607465	chr2:179472194;179472193;179472192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-113
• Domain position: 65
• Structural Position: 153
• Q(SASA): 0.6272
• 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
R/G	rs1189355872	None	0.959	N	0.525	0.452	0.692629309879	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/G	rs1189355872	None	0.959	N	0.525	0.452	0.692629309879	gnomAD-4.0.0	6.578E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47167E-05	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
R/A	0.7105	likely_pathogenic	0.6438	pathogenic	-0.74	Destabilizing	0.863	D	0.513	neutral	None	None	None	None	I
R/C	0.2932	likely_benign	0.2483	benign	-0.7	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	I
R/D	0.8646	likely_pathogenic	0.8359	pathogenic	0.031	Stabilizing	0.969	D	0.543	neutral	None	None	None	None	I
R/E	0.6461	likely_pathogenic	0.6056	pathogenic	0.174	Stabilizing	0.863	D	0.546	neutral	None	None	None	None	I
R/F	0.723	likely_pathogenic	0.6651	pathogenic	-0.423	Destabilizing	0.997	D	0.561	neutral	None	None	None	None	I
R/G	0.6307	likely_pathogenic	0.549	ambiguous	-1.075	Destabilizing	0.959	D	0.525	neutral	N	0.488770656	None	None	I
R/H	0.1728	likely_benign	0.1483	benign	-1.324	Destabilizing	0.997	D	0.575	neutral	None	None	None	None	I
R/I	0.3427	ambiguous	0.3101	benign	0.169	Stabilizing	0.996	D	0.563	neutral	N	0.408671683	None	None	I
R/K	0.1568	likely_benign	0.1434	benign	-0.754	Destabilizing	0.021	N	0.204	neutral	N	0.387736263	None	None	I
R/L	0.3692	ambiguous	0.3222	benign	0.169	Stabilizing	0.969	D	0.525	neutral	None	None	None	None	I
R/M	0.4175	ambiguous	0.3823	ambiguous	-0.255	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	I
R/N	0.7493	likely_pathogenic	0.7007	pathogenic	-0.248	Destabilizing	0.969	D	0.55	neutral	None	None	None	None	I
R/P	0.8928	likely_pathogenic	0.8259	pathogenic	-0.112	Destabilizing	0.997	D	0.557	neutral	None	None	None	None	I
R/Q	0.1833	likely_benign	0.1624	benign	-0.354	Destabilizing	0.939	D	0.576	neutral	None	None	None	None	I
R/S	0.7523	likely_pathogenic	0.6879	pathogenic	-1.011	Destabilizing	0.92	D	0.525	neutral	N	0.455924125	None	None	I
R/T	0.4404	ambiguous	0.3823	ambiguous	-0.677	Destabilizing	0.959	D	0.538	neutral	N	0.421792909	None	None	I
R/V	0.4996	ambiguous	0.4495	ambiguous	-0.112	Destabilizing	0.991	D	0.53	neutral	None	None	None	None	I
R/W	0.2771	likely_benign	0.2413	benign	-0.052	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
R/Y	0.5473	ambiguous	0.4765	ambiguous	0.218	Stabilizing	0.997	D	0.578	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.