TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13720	41383;41384;41385	chr2:178636569;178636568;178636567	chr2:179501296;179501295;179501294
N2AB	12079	36460;36461;36462	chr2:178636569;178636568;178636567	chr2:179501296;179501295;179501294
N2A	11152	33679;33680;33681	chr2:178636569;178636568;178636567	chr2:179501296;179501295;179501294
N2B	4655	14188;14189;14190	chr2:178636569;178636568;178636567	chr2:179501296;179501295;179501294
Novex-1	4780	14563;14564;14565	chr2:178636569;178636568;178636567	chr2:179501296;179501295;179501294
Novex-2	4847	14764;14765;14766	chr2:178636569;178636568;178636567	chr2:179501296;179501295;179501294
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-87
• Domain position: 37
• Structural Position: 49
• Q(SASA): 0.2077
• 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
M/K	rs1490705626	None	0.993	N	0.488	0.499	0.542007956216	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/K	rs1490705626	None	0.993	N	0.488	0.499	0.542007956216	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47076E-05	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
M/A	0.8652	likely_pathogenic	0.9436	pathogenic	-1.504	Destabilizing	0.963	D	0.526	neutral	None	None	None	None	N
M/C	0.9353	likely_pathogenic	0.9614	pathogenic	-1.668	Destabilizing	1.0	D	0.531	neutral	None	None	None	None	N
M/D	0.9928	likely_pathogenic	0.997	pathogenic	-0.734	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
M/E	0.845	likely_pathogenic	0.9204	pathogenic	-0.645	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
M/F	0.5114	ambiguous	0.6086	pathogenic	-0.548	Destabilizing	0.969	D	0.536	neutral	None	None	None	None	N
M/G	0.943	likely_pathogenic	0.9752	pathogenic	-1.868	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
M/H	0.8354	likely_pathogenic	0.9119	pathogenic	-1.222	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
M/I	0.7807	likely_pathogenic	0.8871	pathogenic	-0.541	Destabilizing	0.828	D	0.607	neutral	N	0.446784662	None	None	N
M/K	0.4988	ambiguous	0.6852	pathogenic	-0.394	Destabilizing	0.993	D	0.488	neutral	N	0.440595244	None	None	N
M/L	0.2903	likely_benign	0.381	ambiguous	-0.541	Destabilizing	0.03	N	0.312	neutral	N	0.41059304	None	None	N
M/N	0.8851	likely_pathogenic	0.9376	pathogenic	-0.44	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
M/P	0.9995	likely_pathogenic	0.9998	pathogenic	-0.835	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
M/Q	0.386	ambiguous	0.5227	ambiguous	-0.42	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
M/R	0.5327	ambiguous	0.7445	pathogenic	-0.235	Destabilizing	0.998	D	0.547	neutral	N	0.440297767	None	None	N
M/S	0.8161	likely_pathogenic	0.9185	pathogenic	-1.083	Destabilizing	0.995	D	0.484	neutral	None	None	None	None	N
M/T	0.679	likely_pathogenic	0.8648	pathogenic	-0.869	Destabilizing	0.979	D	0.48	neutral	N	0.44158834	None	None	N
M/V	0.3393	likely_benign	0.5131	ambiguous	-0.835	Destabilizing	0.828	D	0.535	neutral	N	0.44095882	None	None	N
M/W	0.8797	likely_pathogenic	0.9355	pathogenic	-0.628	Destabilizing	1.0	D	0.542	neutral	None	None	None	None	N
M/Y	0.7924	likely_pathogenic	0.8614	pathogenic	-0.521	Destabilizing	0.999	D	0.552	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.