TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22744	68455;68456;68457	chr2:178578710;178578709;178578708	chr2:179443437;179443436;179443435
N2AB	21103	63532;63533;63534	chr2:178578710;178578709;178578708	chr2:179443437;179443436;179443435
N2A	20176	60751;60752;60753	chr2:178578710;178578709;178578708	chr2:179443437;179443436;179443435
N2B	13679	41260;41261;41262	chr2:178578710;178578709;178578708	chr2:179443437;179443436;179443435
Novex-1	13804	41635;41636;41637	chr2:178578710;178578709;178578708	chr2:179443437;179443436;179443435
Novex-2	13871	41836;41837;41838	chr2:178578710;178578709;178578708	chr2:179443437;179443436;179443435
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-53
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3769
• 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
P/R	rs1559481626	None	1.0	D	0.836	0.599	0.524218619521	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
P/R	rs1559481626	None	1.0	D	0.836	0.599	0.524218619521	gnomAD-4.0.0	1.60031E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86674E-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	0.9199	likely_pathogenic	0.8988	pathogenic	-1.601	Destabilizing	0.999	D	0.794	deleterious	D	0.533859347	None	None	I
P/C	0.9939	likely_pathogenic	0.9914	pathogenic	-1.837	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.067	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/E	0.9987	likely_pathogenic	0.9987	pathogenic	-3.008	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/F	0.9998	likely_pathogenic	0.9998	pathogenic	-1.155	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
P/G	0.9963	likely_pathogenic	0.9955	pathogenic	-1.939	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/H	0.9987	likely_pathogenic	0.9987	pathogenic	-1.396	Destabilizing	1.0	D	0.806	deleterious	D	0.5464831	None	None	I
P/I	0.9951	likely_pathogenic	0.995	pathogenic	-0.724	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/K	0.9993	likely_pathogenic	0.9993	pathogenic	-1.435	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
P/L	0.9773	likely_pathogenic	0.9764	pathogenic	-0.724	Destabilizing	1.0	D	0.823	deleterious	D	0.543948205	None	None	I
P/M	0.9975	likely_pathogenic	0.9972	pathogenic	-0.901	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
P/N	0.9996	likely_pathogenic	0.9995	pathogenic	-1.669	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
P/Q	0.9979	likely_pathogenic	0.9978	pathogenic	-1.829	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/R	0.9966	likely_pathogenic	0.9966	pathogenic	-0.976	Destabilizing	1.0	D	0.836	deleterious	D	0.545722632	None	None	I
P/S	0.9928	likely_pathogenic	0.99	pathogenic	-2.039	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.545469142	None	None	I
P/T	0.9886	likely_pathogenic	0.986	pathogenic	-1.876	Destabilizing	1.0	D	0.798	deleterious	D	0.545215653	None	None	I
P/V	0.9835	likely_pathogenic	0.9823	pathogenic	-0.988	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.48	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-1.149	Destabilizing	1.0	D	0.859	deleterious	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.