TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18115	54568;54569;54570	chr2:178604746;178604745;178604744	chr2:179469473;179469472;179469471
N2AB	16474	49645;49646;49647	chr2:178604746;178604745;178604744	chr2:179469473;179469472;179469471
N2A	15547	46864;46865;46866	chr2:178604746;178604745;178604744	chr2:179469473;179469472;179469471
N2B	9050	27373;27374;27375	chr2:178604746;178604745;178604744	chr2:179469473;179469472;179469471
Novex-1	9175	27748;27749;27750	chr2:178604746;178604745;178604744	chr2:179469473;179469472;179469471
Novex-2	9242	27949;27950;27951	chr2:178604746;178604745;178604744	chr2:179469473;179469472;179469471
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-19
• Domain position: 51
• Structural Position: 66
• Q(SASA): 0.6084
• 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
E/D	None	None	0.996	N	0.497	0.132	0.185906805712	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/K	rs2054377809	None	0.996	N	0.527	0.304	0.255777322467	gnomAD-4.0.0	1.59571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86633E-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
E/A	0.3297	likely_benign	0.3011	benign	-0.671	Destabilizing	0.978	D	0.523	neutral	N	0.477266897	None	None	N
E/C	0.9133	likely_pathogenic	0.9055	pathogenic	-0.274	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/D	0.2305	likely_benign	0.2366	benign	-0.656	Destabilizing	0.996	D	0.497	neutral	N	0.476882895	None	None	N
E/F	0.8856	likely_pathogenic	0.8684	pathogenic	-0.368	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/G	0.4363	ambiguous	0.4122	ambiguous	-0.931	Destabilizing	0.999	D	0.565	neutral	N	0.512496979	None	None	N
E/H	0.7106	likely_pathogenic	0.6691	pathogenic	-0.315	Destabilizing	1.0	D	0.57	neutral	None	None	None	None	N
E/I	0.4196	ambiguous	0.3942	ambiguous	0.006	Stabilizing	0.967	D	0.581	neutral	None	None	None	None	N
E/K	0.3843	ambiguous	0.3113	benign	-0.11	Destabilizing	0.996	D	0.527	neutral	N	0.443903685	None	None	N
E/L	0.5473	ambiguous	0.4999	ambiguous	0.006	Stabilizing	0.967	D	0.555	neutral	None	None	None	None	N
E/M	0.5785	likely_pathogenic	0.5462	ambiguous	0.208	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/N	0.464	ambiguous	0.471	ambiguous	-0.495	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
E/P	0.9831	likely_pathogenic	0.9777	pathogenic	-0.199	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/Q	0.226	likely_benign	0.2038	benign	-0.434	Destabilizing	0.999	D	0.563	neutral	N	0.445789197	None	None	N
E/R	0.5709	likely_pathogenic	0.4896	ambiguous	0.172	Stabilizing	0.999	D	0.583	neutral	None	None	None	None	N
E/S	0.404	ambiguous	0.4061	ambiguous	-0.69	Destabilizing	0.992	D	0.529	neutral	None	None	None	None	N
E/T	0.3077	likely_benign	0.3058	benign	-0.482	Destabilizing	0.983	D	0.569	neutral	None	None	None	None	N
E/V	0.2654	likely_benign	0.2368	benign	-0.199	Destabilizing	0.37	N	0.325	neutral	N	0.428704946	None	None	N
E/W	0.967	likely_pathogenic	0.9567	pathogenic	-0.148	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/Y	0.8308	likely_pathogenic	0.8012	pathogenic	-0.123	Destabilizing	0.999	D	0.662	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.