TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1865	5818;5819;5820	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996
N2AB	1865	5818;5819;5820	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996
N2A	1865	5818;5819;5820	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996
N2B	1819	5680;5681;5682	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996
Novex-1	1819	5680;5681;5682	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996
Novex-2	1819	5680;5681;5682	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996
Novex-3	1865	5818;5819;5820	chr2:178776271;178776270;178776269	chr2:179640998;179640997;179640996

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-9
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4053
• 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
T/A	rs2092214772	None	0.999	N	0.445	0.444	0.378674557249	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06782E-04	0
T/A	rs2092214772	None	0.999	N	0.445	0.444	0.378674557249	gnomAD-4.0.0	2.02979E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.20491E-06	4.69572E-05	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
T/A	0.1725	likely_benign	0.2049	benign	-0.641	Destabilizing	0.999	D	0.445	neutral	N	0.508647459	None	None	I
T/C	0.7678	likely_pathogenic	0.8049	pathogenic	-0.386	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
T/D	0.7984	likely_pathogenic	0.8614	pathogenic	0.063	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
T/E	0.6605	likely_pathogenic	0.7504	pathogenic	0.045	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
T/F	0.5515	ambiguous	0.6186	pathogenic	-0.773	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
T/G	0.5229	ambiguous	0.6017	pathogenic	-0.873	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
T/H	0.5827	likely_pathogenic	0.6735	pathogenic	-1.112	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
T/I	0.2957	likely_benign	0.3423	ambiguous	-0.124	Destabilizing	1.0	D	0.695	prob.neutral	N	0.511268854	None	None	I
T/K	0.5517	ambiguous	0.6442	pathogenic	-0.631	Destabilizing	1.0	D	0.699	prob.neutral	N	0.511156116	None	None	I
T/L	0.1951	likely_benign	0.2284	benign	-0.124	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
T/M	0.1419	likely_benign	0.1543	benign	0.02	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	I
T/N	0.2799	likely_benign	0.3396	benign	-0.479	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
T/P	0.7669	likely_pathogenic	0.7908	pathogenic	-0.264	Destabilizing	1.0	D	0.697	prob.neutral	D	0.605136791	None	None	I
T/Q	0.4774	ambiguous	0.576	pathogenic	-0.628	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
T/R	0.4919	ambiguous	0.5768	pathogenic	-0.392	Destabilizing	1.0	D	0.703	prob.neutral	N	0.512751637	None	None	I
T/S	0.2002	likely_benign	0.2403	benign	-0.749	Destabilizing	0.999	D	0.44	neutral	N	0.487479234	None	None	I
T/V	0.2237	likely_benign	0.2536	benign	-0.264	Destabilizing	0.999	D	0.529	neutral	None	None	None	None	I
T/W	0.8835	likely_pathogenic	0.9115	pathogenic	-0.736	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
T/Y	0.7004	likely_pathogenic	0.7534	pathogenic	-0.499	Destabilizing	1.0	D	0.707	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.