TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13921	41986;41987;41988	chr2:178635563;178635562;178635561	chr2:179500290;179500289;179500288
N2AB	12280	37063;37064;37065	chr2:178635563;178635562;178635561	chr2:179500290;179500289;179500288
N2A	11353	34282;34283;34284	chr2:178635563;178635562;178635561	chr2:179500290;179500289;179500288
N2B	4856	14791;14792;14793	chr2:178635563;178635562;178635561	chr2:179500290;179500289;179500288
Novex-1	4981	15166;15167;15168	chr2:178635563;178635562;178635561	chr2:179500290;179500289;179500288
Novex-2	5048	15367;15368;15369	chr2:178635563;178635562;178635561	chr2:179500290;179500289;179500288
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-89
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.2255
• 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
T/A	None	None	0.817	N	0.474	0.152	0.101711395817	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/I	None	None	0.126	N	0.398	0.189	0.186928172975	gnomAD-4.0.0	6.93129E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08001E-07	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
T/A	0.2779	likely_benign	0.3176	benign	-0.877	Destabilizing	0.817	D	0.474	neutral	N	0.470557234	None	None	N
T/C	0.6676	likely_pathogenic	0.6832	pathogenic	-0.792	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
T/D	0.9202	likely_pathogenic	0.9028	pathogenic	-1.646	Destabilizing	0.997	D	0.706	prob.delet.	None	None	None	None	N
T/E	0.8014	likely_pathogenic	0.7804	pathogenic	-1.476	Destabilizing	0.989	D	0.683	prob.neutral	None	None	None	None	N
T/F	0.4651	ambiguous	0.5696	pathogenic	-0.439	Destabilizing	0.877	D	0.685	prob.delet.	None	None	None	None	N
T/G	0.7057	likely_pathogenic	0.7112	pathogenic	-1.283	Destabilizing	0.967	D	0.669	prob.neutral	None	None	None	None	N
T/H	0.6725	likely_pathogenic	0.7177	pathogenic	-1.625	Destabilizing	0.99	D	0.642	neutral	None	None	None	None	N
T/I	0.3099	likely_benign	0.3873	ambiguous	0.172	Stabilizing	0.126	N	0.398	neutral	N	0.441913628	None	None	N
T/K	0.8001	likely_pathogenic	0.7907	pathogenic	-0.947	Destabilizing	0.967	D	0.679	prob.neutral	None	None	None	None	N
T/L	0.2163	likely_benign	0.2454	benign	0.172	Stabilizing	0.563	D	0.533	neutral	None	None	None	None	N
T/M	0.1417	likely_benign	0.159	benign	0.151	Stabilizing	0.563	D	0.486	neutral	None	None	None	None	N
T/N	0.4798	ambiguous	0.4983	ambiguous	-1.526	Destabilizing	0.996	D	0.657	prob.neutral	N	0.474759225	None	None	N
T/P	0.9539	likely_pathogenic	0.9453	pathogenic	-0.145	Destabilizing	0.996	D	0.705	prob.delet.	N	0.476127042	None	None	N
T/Q	0.6711	likely_pathogenic	0.6984	pathogenic	-1.289	Destabilizing	0.99	D	0.691	prob.delet.	None	None	None	None	N
T/R	0.7269	likely_pathogenic	0.7293	pathogenic	-1.159	Destabilizing	0.99	D	0.704	prob.delet.	None	None	None	None	N
T/S	0.3922	ambiguous	0.4047	ambiguous	-1.607	Destabilizing	0.956	D	0.57	neutral	N	0.473744532	None	None	N
T/V	0.2267	likely_benign	0.2828	benign	-0.145	Destabilizing	0.075	N	0.215	neutral	None	None	None	None	N
T/W	0.8095	likely_pathogenic	0.8414	pathogenic	-0.704	Destabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
T/Y	0.4865	ambiguous	0.5605	ambiguous	-0.334	Destabilizing	0.161	N	0.549	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.