TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31432	94519;94520;94521	chr2:178547231;178547230;178547229	chr2:179411958;179411957;179411956
N2AB	29791	89596;89597;89598	chr2:178547231;178547230;178547229	chr2:179411958;179411957;179411956
N2A	28864	86815;86816;86817	chr2:178547231;178547230;178547229	chr2:179411958;179411957;179411956
N2B	22367	67324;67325;67326	chr2:178547231;178547230;178547229	chr2:179411958;179411957;179411956
Novex-1	22492	67699;67700;67701	chr2:178547231;178547230;178547229	chr2:179411958;179411957;179411956
Novex-2	22559	67900;67901;67902	chr2:178547231;178547230;178547229	chr2:179411958;179411957;179411956
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-117
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1399
• 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	rs759415579	-0.488	1.0	D	0.898	0.62	0.904311493753	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.61472E-04	None	0	0	0
P/L	rs759415579	-0.488	1.0	D	0.898	0.62	0.904311493753	gnomAD-4.0.0	1.43685E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31879E-04	1.65662E-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
P/A	0.7912	likely_pathogenic	0.8353	pathogenic	-1.883	Destabilizing	1.0	D	0.834	deleterious	D	0.581364862	None	None	N
P/C	0.9709	likely_pathogenic	0.9815	pathogenic	-1.247	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/D	0.9977	likely_pathogenic	0.9979	pathogenic	-2.344	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/E	0.997	likely_pathogenic	0.9972	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9996	pathogenic	-1.237	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/G	0.9773	likely_pathogenic	0.9809	pathogenic	-2.344	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/H	0.9955	likely_pathogenic	0.9965	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.635368145	None	None	N
P/I	0.9924	likely_pathogenic	0.9939	pathogenic	-0.638	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/K	0.9985	likely_pathogenic	0.9986	pathogenic	-1.573	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/L	0.9763	likely_pathogenic	0.9809	pathogenic	-0.638	Destabilizing	1.0	D	0.898	deleterious	D	0.618339763	None	None	N
P/M	0.9941	likely_pathogenic	0.9959	pathogenic	-0.502	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/N	0.995	likely_pathogenic	0.9959	pathogenic	-1.653	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/Q	0.995	likely_pathogenic	0.9958	pathogenic	-1.632	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/R	0.9957	likely_pathogenic	0.9961	pathogenic	-1.261	Destabilizing	1.0	D	0.898	deleterious	D	0.609628229	None	None	N
P/S	0.9488	likely_pathogenic	0.9595	pathogenic	-2.209	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.564709728	None	None	N
P/T	0.9543	likely_pathogenic	0.959	pathogenic	-1.949	Destabilizing	1.0	D	0.857	deleterious	D	0.60269365	None	None	N
P/V	0.9722	likely_pathogenic	0.9765	pathogenic	-1.023	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9999	pathogenic	-1.719	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9996	pathogenic	-1.338	Destabilizing	1.0	D	0.901	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.