TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26034	78325;78326;78327	chr2:178568032;178568031;178568030	chr2:179432759;179432758;179432757
N2AB	24393	73402;73403;73404	chr2:178568032;178568031;178568030	chr2:179432759;179432758;179432757
N2A	23466	70621;70622;70623	chr2:178568032;178568031;178568030	chr2:179432759;179432758;179432757
N2B	16969	51130;51131;51132	chr2:178568032;178568031;178568030	chr2:179432759;179432758;179432757
Novex-1	17094	51505;51506;51507	chr2:178568032;178568031;178568030	chr2:179432759;179432758;179432757
Novex-2	17161	51706;51707;51708	chr2:178568032;178568031;178568030	chr2:179432759;179432758;179432757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-77
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3546
• 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/N	None	None	0.983	N	0.451	0.204	0.186928172975	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2014	likely_benign	0.2558	benign	-0.345	Destabilizing	0.033	N	0.278	neutral	None	None	None	None	N
S/C	0.3335	likely_benign	0.396	ambiguous	-0.328	Destabilizing	0.995	D	0.528	neutral	N	0.511300278	None	None	N
S/D	0.967	likely_pathogenic	0.9767	pathogenic	0.099	Stabilizing	0.957	D	0.387	neutral	None	None	None	None	N
S/E	0.9808	likely_pathogenic	0.986	pathogenic	0.017	Stabilizing	0.916	D	0.355	neutral	None	None	None	None	N
S/F	0.9116	likely_pathogenic	0.9403	pathogenic	-0.813	Destabilizing	0.987	D	0.565	neutral	None	None	None	None	N
S/G	0.185	likely_benign	0.2341	benign	-0.483	Destabilizing	0.805	D	0.351	neutral	N	0.518228086	None	None	N
S/H	0.9235	likely_pathogenic	0.9353	pathogenic	-0.93	Destabilizing	0.999	D	0.512	neutral	None	None	None	None	N
S/I	0.9038	likely_pathogenic	0.9326	pathogenic	-0.111	Destabilizing	0.967	D	0.543	neutral	N	0.515655144	None	None	N
S/K	0.9936	likely_pathogenic	0.9947	pathogenic	-0.597	Destabilizing	0.916	D	0.349	neutral	None	None	None	None	N
S/L	0.5451	ambiguous	0.6284	pathogenic	-0.111	Destabilizing	0.845	D	0.407	neutral	None	None	None	None	N
S/M	0.6926	likely_pathogenic	0.7603	pathogenic	0.055	Stabilizing	0.999	D	0.509	neutral	None	None	None	None	N
S/N	0.6759	likely_pathogenic	0.7465	pathogenic	-0.326	Destabilizing	0.983	D	0.451	neutral	N	0.465706791	None	None	N
S/P	0.993	likely_pathogenic	0.9953	pathogenic	-0.159	Destabilizing	0.987	D	0.482	neutral	None	None	None	None	N
S/Q	0.9521	likely_pathogenic	0.9583	pathogenic	-0.557	Destabilizing	0.987	D	0.445	neutral	None	None	None	None	N
S/R	0.9871	likely_pathogenic	0.9887	pathogenic	-0.358	Destabilizing	0.983	D	0.47	neutral	N	0.487636161	None	None	N
S/T	0.2805	likely_benign	0.3205	benign	-0.423	Destabilizing	0.892	D	0.345	neutral	N	0.510744753	None	None	N
S/V	0.8312	likely_pathogenic	0.8729	pathogenic	-0.159	Destabilizing	0.95	D	0.486	neutral	None	None	None	None	N
S/W	0.9584	likely_pathogenic	0.9688	pathogenic	-0.823	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
S/Y	0.8777	likely_pathogenic	0.9061	pathogenic	-0.56	Destabilizing	0.996	D	0.572	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.