TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18603	56032;56033;56034	chr2:178601097;178601096;178601095	chr2:179465824;179465823;179465822
N2AB	16962	51109;51110;51111	chr2:178601097;178601096;178601095	chr2:179465824;179465823;179465822
N2A	16035	48328;48329;48330	chr2:178601097;178601096;178601095	chr2:179465824;179465823;179465822
N2B	9538	28837;28838;28839	chr2:178601097;178601096;178601095	chr2:179465824;179465823;179465822
Novex-1	9663	29212;29213;29214	chr2:178601097;178601096;178601095	chr2:179465824;179465823;179465822
Novex-2	9730	29413;29414;29415	chr2:178601097;178601096;178601095	chr2:179465824;179465823;179465822
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Fn3-23
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1366
• 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
P/L	rs531760043	-0.599	0.996	D	0.889	0.651	0.873394877099	gnomAD-2.1.1	2.09E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.49E-05	None	0	3.7E-05	0
P/L	rs531760043	-0.599	0.996	D	0.889	0.651	0.873394877099	gnomAD-4.0.0	9.64776E-06	None	None	None	None	N	None	0	2.2853E-05	None	0	0	None	0	0	9.94259E-06	2.36423E-05	0
P/S	None	None	0.284	D	0.56	0.524	0.362361684037	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
P/A	0.9057	likely_pathogenic	0.8842	pathogenic	-2.054	Highly Destabilizing	0.865	D	0.705	prob.neutral	D	0.560702208	None	None	N
P/C	0.9886	likely_pathogenic	0.9872	pathogenic	-1.558	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
P/D	0.9992	likely_pathogenic	0.9994	pathogenic	-3.131	Highly Destabilizing	0.983	D	0.825	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.998	pathogenic	-2.977	Highly Destabilizing	0.983	D	0.821	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9995	pathogenic	-1.254	Destabilizing	0.998	D	0.909	deleterious	None	None	None	None	N
P/G	0.989	likely_pathogenic	0.9894	pathogenic	-2.503	Highly Destabilizing	0.895	D	0.801	deleterious	None	None	None	None	N
P/H	0.9961	likely_pathogenic	0.9959	pathogenic	-2.422	Highly Destabilizing	0.998	D	0.89	deleterious	None	None	None	None	N
P/I	0.9964	likely_pathogenic	0.9955	pathogenic	-0.813	Destabilizing	0.992	D	0.898	deleterious	None	None	None	None	N
P/K	0.9981	likely_pathogenic	0.9984	pathogenic	-1.892	Destabilizing	0.968	D	0.826	deleterious	None	None	None	None	N
P/L	0.9832	likely_pathogenic	0.978	pathogenic	-0.813	Destabilizing	0.996	D	0.889	deleterious	D	0.613696469	None	None	N
P/M	0.9975	likely_pathogenic	0.9971	pathogenic	-0.725	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
P/N	0.9987	likely_pathogenic	0.999	pathogenic	-2.082	Highly Destabilizing	0.968	D	0.891	deleterious	None	None	None	None	N
P/Q	0.9939	likely_pathogenic	0.9942	pathogenic	-2.01	Highly Destabilizing	0.991	D	0.837	deleterious	D	0.614705491	None	None	N
P/R	0.9913	likely_pathogenic	0.9914	pathogenic	-1.582	Destabilizing	0.991	D	0.883	deleterious	D	0.579446824	None	None	N
P/S	0.9775	likely_pathogenic	0.9763	pathogenic	-2.518	Highly Destabilizing	0.284	N	0.56	neutral	D	0.541957592	None	None	N
P/T	0.9813	likely_pathogenic	0.9796	pathogenic	-2.261	Highly Destabilizing	0.957	D	0.802	deleterious	D	0.592942734	None	None	N
P/V	0.9856	likely_pathogenic	0.9813	pathogenic	-1.203	Destabilizing	0.983	D	0.877	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.89	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
P/Y	0.9995	likely_pathogenic	0.9995	pathogenic	-1.558	Destabilizing	0.999	D	0.907	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.