TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16662	50209;50210;50211	chr2:178612541;178612540;178612539	chr2:179477268;179477267;179477266
N2AB	15021	45286;45287;45288	chr2:178612541;178612540;178612539	chr2:179477268;179477267;179477266
N2A	14094	42505;42506;42507	chr2:178612541;178612540;178612539	chr2:179477268;179477267;179477266
N2B	7597	23014;23015;23016	chr2:178612541;178612540;178612539	chr2:179477268;179477267;179477266
Novex-1	7722	23389;23390;23391	chr2:178612541;178612540;178612539	chr2:179477268;179477267;179477266
Novex-2	7789	23590;23591;23592	chr2:178612541;178612540;178612539	chr2:179477268;179477267;179477266
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-9
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.569
• 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
N/D	rs2056522991	None	0.978	N	0.471	0.357	0.181679512989	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
N/D	rs2056522991	None	0.978	N	0.471	0.357	0.181679512989	gnomAD-4.0.0	6.58623E-06	None	None	None	None	N	None	0	6.56254E-05	None	0	0	None	0	0	0	0	0
N/S	rs36043230	0.074	0.63	N	0.166	0.133	0.128392430309	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	6.61E-05	0	None	0	0	None	0	None	0	0	0
N/S	rs36043230	0.074	0.63	N	0.166	0.133	0.128392430309	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.42E-05	6.56E-05	0	0	0	None	0	0	0	0	0
N/S	rs36043230	0.074	0.63	N	0.166	0.133	0.128392430309	gnomAD-4.0.0	1.86158E-06	None	None	None	None	N	None	2.67373E-05	1.67107E-05	None	0	0	None	0	0	0	0	0
N/T	rs36043230	0.272	0.956	N	0.465	0.328	None	gnomAD-2.1.1	1.57647E-02	None	None	None	None	N	None	2.89551E-03	9.19212E-03	None	5.50089E-02	5.24E-05	None	7.7652E-03	None	1.42456E-02	2.1363E-02	1.94675E-02
N/T	rs36043230	0.272	0.956	N	0.465	0.328	None	gnomAD-3.1.2	1.43738E-02	None	None	None	None	N	None	3.62336E-03	1.10265E-02	4.38597E-03	5.33449E-02	0	None	1.39754E-02	2.8481E-02	2.12475E-02	6.42354E-03	2.15517E-02
N/T	rs36043230	0.272	0.956	N	0.465	0.328	None	1000 genomes	6.38978E-03	None	None	None	None	N	None	2.3E-03	8.6E-03	None	None	0	1.69E-02	None	None	None	6.1E-03	None
N/T	rs36043230	0.272	0.956	N	0.465	0.328	None	gnomAD-4.0.0	1.95167E-02	None	None	None	None	N	None	3.33672E-03	1.0441E-02	None	5.31584E-02	2.24578E-05	None	1.42754E-02	3.25728E-02	2.1871E-02	8.08048E-03	2.20954E-02

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
N/A	0.4838	ambiguous	0.4129	ambiguous	-0.383	Destabilizing	0.967	D	0.455	neutral	None	None	None	None	N
N/C	0.6702	likely_pathogenic	0.6161	pathogenic	0.31	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
N/D	0.3605	ambiguous	0.4113	ambiguous	0.192	Stabilizing	0.978	D	0.471	neutral	N	0.39539209	None	None	N
N/E	0.6994	likely_pathogenic	0.7722	pathogenic	0.165	Stabilizing	0.983	D	0.51	neutral	None	None	None	None	N
N/F	0.9016	likely_pathogenic	0.8927	pathogenic	-0.704	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
N/G	0.4643	ambiguous	0.3976	ambiguous	-0.57	Destabilizing	0.983	D	0.463	neutral	None	None	None	None	N
N/H	0.2109	likely_benign	0.2214	benign	-0.564	Destabilizing	0.999	D	0.572	neutral	N	0.485618798	None	None	N
N/I	0.7759	likely_pathogenic	0.7298	pathogenic	0.022	Stabilizing	0.997	D	0.68	prob.neutral	N	0.520468615	None	None	N
N/K	0.6962	likely_pathogenic	0.7805	pathogenic	0.12	Stabilizing	0.978	D	0.523	neutral	N	0.483358926	None	None	N
N/L	0.6694	likely_pathogenic	0.6432	pathogenic	0.022	Stabilizing	0.998	D	0.613	neutral	None	None	None	None	N
N/M	0.7861	likely_pathogenic	0.7351	pathogenic	0.36	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	N
N/P	0.9672	likely_pathogenic	0.9698	pathogenic	-0.086	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
N/Q	0.6163	likely_pathogenic	0.6417	pathogenic	-0.369	Destabilizing	0.998	D	0.598	neutral	None	None	None	None	N
N/R	0.676	likely_pathogenic	0.7686	pathogenic	0.163	Stabilizing	0.998	D	0.588	neutral	None	None	None	None	N
N/S	0.1114	likely_benign	0.0943	benign	-0.173	Destabilizing	0.63	D	0.166	neutral	N	0.461722907	None	None	N
N/T	0.2553	likely_benign	0.2119	benign	-0.047	Destabilizing	0.956	D	0.465	neutral	N	0.478025906	None	None	N
N/V	0.7046	likely_pathogenic	0.6447	pathogenic	-0.086	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
N/W	0.9635	likely_pathogenic	0.9676	pathogenic	-0.653	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
N/Y	0.5712	likely_pathogenic	0.5805	pathogenic	-0.395	Destabilizing	0.999	D	0.639	neutral	N	0.500152606	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.