TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6990	21193;21194;21195	chr2:178724407;178724406;178724405	chr2:179589134;179589133;179589132
N2AB	6673	20242;20243;20244	chr2:178724407;178724406;178724405	chr2:179589134;179589133;179589132
N2A	5746	17461;17462;17463	chr2:178724407;178724406;178724405	chr2:179589134;179589133;179589132
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-54
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4377
• 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
S/G	rs1467185474	-0.248	0.994	N	0.39	0.383	0.267299060538	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
S/G	rs1467185474	-0.248	0.994	N	0.39	0.383	0.267299060538	gnomAD-4.0.0	3.18377E-06	None	None	None	None	N	None	5.66316E-05	0	None	0	0	None	0	0	2.85959E-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
S/A	0.0733	likely_benign	0.079	benign	-0.418	Destabilizing	0.99	D	0.389	neutral	None	None	None	None	N
S/C	0.2109	likely_benign	0.2302	benign	-0.343	Destabilizing	1.0	D	0.651	neutral	N	0.505601599	None	None	N
S/D	0.3486	ambiguous	0.3983	ambiguous	0.428	Stabilizing	0.269	N	0.245	neutral	None	None	None	None	N
S/E	0.4629	ambiguous	0.5362	ambiguous	0.341	Stabilizing	0.983	D	0.397	neutral	None	None	None	None	N
S/F	0.2249	likely_benign	0.2563	benign	-1.027	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
S/G	0.0979	likely_benign	0.0937	benign	-0.523	Destabilizing	0.994	D	0.39	neutral	N	0.471936514	None	None	N
S/H	0.3914	ambiguous	0.4381	ambiguous	-0.94	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
S/I	0.2093	likely_benign	0.2263	benign	-0.271	Destabilizing	0.999	D	0.689	prob.neutral	N	0.494101298	None	None	N
S/K	0.6271	likely_pathogenic	0.6933	pathogenic	-0.382	Destabilizing	0.996	D	0.465	neutral	None	None	None	None	N
S/L	0.1225	likely_benign	0.1344	benign	-0.271	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
S/M	0.2615	likely_benign	0.273	benign	-0.15	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
S/N	0.1596	likely_benign	0.1565	benign	-0.148	Destabilizing	0.989	D	0.421	neutral	N	0.46198888	None	None	N
S/P	0.0969	likely_benign	0.1071	benign	-0.292	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
S/Q	0.4955	ambiguous	0.5441	ambiguous	-0.344	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
S/R	0.5455	ambiguous	0.6139	pathogenic	-0.208	Destabilizing	0.998	D	0.684	prob.neutral	N	0.484788382	None	None	N
S/T	0.0983	likely_benign	0.0946	benign	-0.278	Destabilizing	0.994	D	0.387	neutral	N	0.465682546	None	None	N
S/V	0.1922	likely_benign	0.2098	benign	-0.292	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
S/W	0.3472	ambiguous	0.3978	ambiguous	-1.04	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
S/Y	0.1946	likely_benign	0.2293	benign	-0.749	Destabilizing	1.0	D	0.682	prob.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.