TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10154	30685;30686;30687	chr2:178702219;178702218;178702217	chr2:179566946;179566945;179566944
N2AB	9837	29734;29735;29736	chr2:178702219;178702218;178702217	chr2:179566946;179566945;179566944
N2A	8910	26953;26954;26955	chr2:178702219;178702218;178702217	chr2:179566946;179566945;179566944
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-86
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.6605
• 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
E/G	rs761055099	-0.628	1.0	None	0.641	0.4	0.260249123532	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
E/G	rs761055099	-0.628	1.0	None	0.641	0.4	0.260249123532	gnomAD-4.0.0	1.59085E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85745E-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
E/A	0.5012	ambiguous	0.5155	ambiguous	-0.165	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
E/C	0.9868	likely_pathogenic	0.9877	pathogenic	-0.242	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/D	0.6107	likely_pathogenic	0.6257	pathogenic	-0.334	Destabilizing	0.999	D	0.515	neutral	None	None	None	None	I
E/F	0.9489	likely_pathogenic	0.9473	pathogenic	-0.007	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/G	0.643	likely_pathogenic	0.6475	pathogenic	-0.334	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
E/H	0.8908	likely_pathogenic	0.8921	pathogenic	0.521	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
E/I	0.8738	likely_pathogenic	0.8882	pathogenic	0.238	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/K	0.7423	likely_pathogenic	0.7362	pathogenic	0.4	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	I
E/L	0.8226	likely_pathogenic	0.8272	pathogenic	0.238	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/M	0.8867	likely_pathogenic	0.8942	pathogenic	0.049	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
E/N	0.8381	likely_pathogenic	0.8489	pathogenic	-0.041	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/P	0.7178	likely_pathogenic	0.709	pathogenic	0.123	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
E/Q	0.476	ambiguous	0.4849	ambiguous	0.012	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/R	0.8102	likely_pathogenic	0.8027	pathogenic	0.698	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
E/S	0.6213	likely_pathogenic	0.6377	pathogenic	-0.158	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
E/T	0.7828	likely_pathogenic	0.7971	pathogenic	-0.007	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/V	0.7504	likely_pathogenic	0.767	pathogenic	0.123	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/W	0.984	likely_pathogenic	0.9821	pathogenic	0.119	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/Y	0.9109	likely_pathogenic	0.9078	pathogenic	0.233	Stabilizing	1.0	D	0.693	prob.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.