TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22791	68596;68597;68598	chr2:178578144;178578143;178578142	chr2:179442871;179442870;179442869
N2AB	21150	63673;63674;63675	chr2:178578144;178578143;178578142	chr2:179442871;179442870;179442869
N2A	20223	60892;60893;60894	chr2:178578144;178578143;178578142	chr2:179442871;179442870;179442869
N2B	13726	41401;41402;41403	chr2:178578144;178578143;178578142	chr2:179442871;179442870;179442869
Novex-1	13851	41776;41777;41778	chr2:178578144;178578143;178578142	chr2:179442871;179442870;179442869
Novex-2	13918	41977;41978;41979	chr2:178578144;178578143;178578142	chr2:179442871;179442870;179442869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-53
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3272
• 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
K/R	rs774260031	-0.077	0.822	N	0.496	0.239	0.18995819373	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
K/R	rs774260031	-0.077	0.822	N	0.496	0.239	0.18995819373	gnomAD-4.0.0	2.19053E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87924E-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
K/A	0.7873	likely_pathogenic	0.7699	pathogenic	-0.686	Destabilizing	0.754	D	0.457	neutral	None	None	None	None	I
K/C	0.8235	likely_pathogenic	0.8105	pathogenic	-0.741	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
K/D	0.9148	likely_pathogenic	0.9123	pathogenic	-0.203	Destabilizing	0.754	D	0.503	neutral	None	None	None	None	I
K/E	0.5381	ambiguous	0.494	ambiguous	-0.035	Destabilizing	0.014	N	0.266	neutral	N	0.437481932	None	None	I
K/F	0.93	likely_pathogenic	0.9225	pathogenic	-0.199	Destabilizing	0.956	D	0.667	neutral	None	None	None	None	I
K/G	0.8238	likely_pathogenic	0.8163	pathogenic	-1.07	Destabilizing	0.86	D	0.509	neutral	None	None	None	None	I
K/H	0.4476	ambiguous	0.4382	ambiguous	-1.004	Destabilizing	0.994	D	0.58	neutral	None	None	None	None	I
K/I	0.6515	likely_pathogenic	0.6132	pathogenic	0.33	Stabilizing	0.915	D	0.595	neutral	None	None	None	None	I
K/L	0.6469	likely_pathogenic	0.6181	pathogenic	0.33	Stabilizing	0.754	D	0.483	neutral	None	None	None	None	I
K/M	0.4924	ambiguous	0.4526	ambiguous	-0.08	Destabilizing	0.992	D	0.58	neutral	N	0.429825241	None	None	I
K/N	0.7801	likely_pathogenic	0.76	pathogenic	-0.698	Destabilizing	0.942	D	0.511	neutral	N	0.482520789	None	None	I
K/P	0.9818	likely_pathogenic	0.9827	pathogenic	0.019	Stabilizing	0.978	D	0.583	neutral	None	None	None	None	I
K/Q	0.2242	likely_benign	0.1953	benign	-0.609	Destabilizing	0.89	D	0.527	neutral	N	0.392381574	None	None	I
K/R	0.1	likely_benign	0.0967	benign	-0.39	Destabilizing	0.822	D	0.496	neutral	N	0.42951581	None	None	I
K/S	0.7968	likely_pathogenic	0.7718	pathogenic	-1.32	Destabilizing	0.86	D	0.489	neutral	None	None	None	None	I
K/T	0.4816	ambiguous	0.4414	ambiguous	-0.933	Destabilizing	0.822	D	0.505	neutral	N	0.373758528	None	None	I
K/V	0.5839	likely_pathogenic	0.5423	ambiguous	0.019	Stabilizing	0.043	N	0.314	neutral	None	None	None	None	I
K/W	0.8944	likely_pathogenic	0.8934	pathogenic	-0.131	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
K/Y	0.8291	likely_pathogenic	0.8266	pathogenic	0.15	Stabilizing	0.978	D	0.635	neutral	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.