TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28293	85102;85103;85104	chr2:178561255;178561254;178561253	chr2:179425982;179425981;179425980
N2AB	26652	80179;80180;80181	chr2:178561255;178561254;178561253	chr2:179425982;179425981;179425980
N2A	25725	77398;77399;77400	chr2:178561255;178561254;178561253	chr2:179425982;179425981;179425980
N2B	19228	57907;57908;57909	chr2:178561255;178561254;178561253	chr2:179425982;179425981;179425980
Novex-1	19353	58282;58283;58284	chr2:178561255;178561254;178561253	chr2:179425982;179425981;179425980
Novex-2	19420	58483;58484;58485	chr2:178561255;178561254;178561253	chr2:179425982;179425981;179425980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-94
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3721
• 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/G	rs879026651	None	0.988	N	0.612	0.479	None	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85811E-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	0.2051	likely_benign	0.1798	benign	-0.959	Destabilizing	0.919	D	0.493	neutral	N	0.48014465	None	None	N
E/C	0.9032	likely_pathogenic	0.8751	pathogenic	-0.586	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/D	0.1446	likely_benign	0.1321	benign	-1.374	Destabilizing	0.958	D	0.374	neutral	N	0.449064363	None	None	N
E/F	0.8579	likely_pathogenic	0.8195	pathogenic	-0.387	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/G	0.3226	likely_benign	0.2951	benign	-1.371	Destabilizing	0.988	D	0.612	neutral	N	0.481158608	None	None	N
E/H	0.6955	likely_pathogenic	0.6401	pathogenic	-0.746	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/I	0.4762	ambiguous	0.3939	ambiguous	0.182	Stabilizing	0.995	D	0.789	deleterious	None	None	None	None	N
E/K	0.3849	ambiguous	0.3006	benign	-0.953	Destabilizing	0.067	N	0.245	neutral	N	0.473882663	None	None	N
E/L	0.4581	ambiguous	0.4033	ambiguous	0.182	Stabilizing	0.991	D	0.751	deleterious	None	None	None	None	N
E/M	0.5508	ambiguous	0.489	ambiguous	0.734	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/N	0.3694	ambiguous	0.316	benign	-1.386	Destabilizing	0.991	D	0.637	neutral	None	None	None	None	N
E/P	0.565	likely_pathogenic	0.4557	ambiguous	-0.177	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
E/Q	0.2341	likely_benign	0.1999	benign	-1.208	Destabilizing	0.958	D	0.553	neutral	N	0.471128522	None	None	N
E/R	0.557	ambiguous	0.4721	ambiguous	-0.705	Destabilizing	0.982	D	0.625	neutral	None	None	None	None	N
E/S	0.311	likely_benign	0.2721	benign	-1.816	Destabilizing	0.968	D	0.499	neutral	None	None	None	None	N
E/T	0.4094	ambiguous	0.3468	ambiguous	-1.468	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	N
E/V	0.2845	likely_benign	0.2338	benign	-0.177	Destabilizing	0.988	D	0.727	prob.delet.	N	0.468979382	None	None	N
E/W	0.9571	likely_pathogenic	0.9392	pathogenic	-0.199	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/Y	0.7868	likely_pathogenic	0.7388	pathogenic	-0.144	Destabilizing	0.998	D	0.743	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.