TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23197	69814;69815;69816	chr2:178576655;178576654;178576653	chr2:179441382;179441381;179441380
N2AB	21556	64891;64892;64893	chr2:178576655;178576654;178576653	chr2:179441382;179441381;179441380
N2A	20629	62110;62111;62112	chr2:178576655;178576654;178576653	chr2:179441382;179441381;179441380
N2B	14132	42619;42620;42621	chr2:178576655;178576654;178576653	chr2:179441382;179441381;179441380
Novex-1	14257	42994;42995;42996	chr2:178576655;178576654;178576653	chr2:179441382;179441381;179441380
Novex-2	14324	43195;43196;43197	chr2:178576655;178576654;178576653	chr2:179441382;179441381;179441380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-56
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.3194
• 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
L/F	rs2046500337	None	0.994	N	0.742	0.206	0.521122704751	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	1.90042E-04	0	None	0	0	None	0	0	0	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
L/A	0.5971	likely_pathogenic	0.5739	pathogenic	-1.854	Destabilizing	0.938	D	0.58	neutral	None	None	None	None	N
L/C	0.597	likely_pathogenic	0.5894	pathogenic	-1.053	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/D	0.9483	likely_pathogenic	0.933	pathogenic	-1.805	Destabilizing	0.991	D	0.79	deleterious	None	None	None	None	N
L/E	0.7513	likely_pathogenic	0.7407	pathogenic	-1.637	Destabilizing	0.991	D	0.784	deleterious	None	None	None	None	N
L/F	0.4864	ambiguous	0.445	ambiguous	-1.071	Destabilizing	0.994	D	0.742	deleterious	N	0.475644291	None	None	N
L/G	0.7624	likely_pathogenic	0.7492	pathogenic	-2.313	Highly Destabilizing	0.991	D	0.781	deleterious	None	None	None	None	N
L/H	0.5977	likely_pathogenic	0.5656	pathogenic	-1.564	Destabilizing	0.999	D	0.794	deleterious	N	0.471783177	None	None	N
L/I	0.2227	likely_benign	0.2165	benign	-0.576	Destabilizing	0.958	D	0.511	neutral	N	0.514822421	None	None	N
L/K	0.5152	ambiguous	0.5187	ambiguous	-1.343	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
L/M	0.1856	likely_benign	0.1774	benign	-0.476	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
L/N	0.6	likely_pathogenic	0.5646	pathogenic	-1.576	Destabilizing	0.991	D	0.785	deleterious	None	None	None	None	N
L/P	0.6602	likely_pathogenic	0.6638	pathogenic	-0.978	Destabilizing	0.994	D	0.793	deleterious	N	0.502893274	None	None	N
L/Q	0.3322	likely_benign	0.337	benign	-1.522	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/R	0.3434	ambiguous	0.3563	ambiguous	-0.992	Destabilizing	0.988	D	0.757	deleterious	N	0.470954214	None	None	N
L/S	0.6568	likely_pathogenic	0.6143	pathogenic	-2.221	Highly Destabilizing	0.982	D	0.725	prob.delet.	None	None	None	None	N
L/T	0.2576	likely_benign	0.2353	benign	-1.916	Destabilizing	0.18	N	0.351	neutral	None	None	None	None	N
L/V	0.1749	likely_benign	0.1703	benign	-0.978	Destabilizing	0.919	D	0.564	neutral	N	0.517169293	None	None	N
L/W	0.6909	likely_pathogenic	0.6594	pathogenic	-1.366	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/Y	0.768	likely_pathogenic	0.7304	pathogenic	-1.021	Destabilizing	0.998	D	0.791	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.