TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31975	96148;96149;96150	chr2:178544306;178544305;178544304	chr2:179409033;179409032;179409031
N2AB	30334	91225;91226;91227	chr2:178544306;178544305;178544304	chr2:179409033;179409032;179409031
N2A	29407	88444;88445;88446	chr2:178544306;178544305;178544304	chr2:179409033;179409032;179409031
N2B	22910	68953;68954;68955	chr2:178544306;178544305;178544304	chr2:179409033;179409032;179409031
Novex-1	23035	69328;69329;69330	chr2:178544306;178544305;178544304	chr2:179409033;179409032;179409031
Novex-2	23102	69529;69530;69531	chr2:178544306;178544305;178544304	chr2:179409033;179409032;179409031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-121
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.0939
• 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
L/F	rs757718784	-2.066	0.999	D	0.831	0.521	0.845547681124	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/F	rs757718784	-2.066	0.999	D	0.831	0.521	0.845547681124	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
L/A	0.9199	likely_pathogenic	0.9167	pathogenic	-2.617	Highly Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
L/C	0.8077	likely_pathogenic	0.8312	pathogenic	-1.859	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9985	pathogenic	-3.161	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/E	0.9929	likely_pathogenic	0.9901	pathogenic	-2.969	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/F	0.8419	likely_pathogenic	0.8084	pathogenic	-1.68	Destabilizing	0.999	D	0.831	deleterious	D	0.644777917	None	None	N
L/G	0.9806	likely_pathogenic	0.9775	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/H	0.988	likely_pathogenic	0.9815	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.831	deleterious	D	0.661604495	None	None	N
L/I	0.3156	likely_benign	0.2913	benign	-1.136	Destabilizing	0.884	D	0.615	neutral	D	0.614748314	None	None	N
L/K	0.9838	likely_pathogenic	0.9739	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/M	0.3989	ambiguous	0.3911	ambiguous	-0.955	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/N	0.9909	likely_pathogenic	0.9889	pathogenic	-2.44	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/P	0.9919	likely_pathogenic	0.9876	pathogenic	-1.61	Destabilizing	1.0	D	0.856	deleterious	D	0.661604495	None	None	N
L/Q	0.9703	likely_pathogenic	0.9587	pathogenic	-2.367	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/R	0.9688	likely_pathogenic	0.9498	pathogenic	-1.748	Destabilizing	1.0	D	0.839	deleterious	D	0.661604495	None	None	N
L/S	0.9867	likely_pathogenic	0.9843	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/T	0.9255	likely_pathogenic	0.9145	pathogenic	-2.737	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/V	0.326	likely_benign	0.3097	benign	-1.61	Destabilizing	0.981	D	0.823	deleterious	D	0.586999279	None	None	N
L/W	0.9804	likely_pathogenic	0.9697	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/Y	0.9842	likely_pathogenic	0.9778	pathogenic	-1.839	Destabilizing	1.0	D	0.815	deleterious	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.