TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26296	79111;79112;79113	chr2:178567246;178567245;178567244	chr2:179431973;179431972;179431971
N2AB	24655	74188;74189;74190	chr2:178567246;178567245;178567244	chr2:179431973;179431972;179431971
N2A	23728	71407;71408;71409	chr2:178567246;178567245;178567244	chr2:179431973;179431972;179431971
N2B	17231	51916;51917;51918	chr2:178567246;178567245;178567244	chr2:179431973;179431972;179431971
Novex-1	17356	52291;52292;52293	chr2:178567246;178567245;178567244	chr2:179431973;179431972;179431971
Novex-2	17423	52492;52493;52494	chr2:178567246;178567245;178567244	chr2:179431973;179431972;179431971
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-79
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.205
• 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
V/I	rs754938831	-0.316	0.025	N	0.219	0.066	0.28492961333	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.08E-06	0
V/I	rs754938831	-0.316	0.025	N	0.219	0.066	0.28492961333	gnomAD-4.0.0	1.6098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88652E-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
V/A	0.6555	likely_pathogenic	0.6169	pathogenic	-1.346	Destabilizing	0.892	D	0.523	neutral	N	0.513190412	None	None	N
V/C	0.8628	likely_pathogenic	0.8618	pathogenic	-1.221	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
V/D	0.9759	likely_pathogenic	0.9684	pathogenic	-0.566	Destabilizing	0.994	D	0.868	deleterious	N	0.515764638	None	None	N
V/E	0.9432	likely_pathogenic	0.9263	pathogenic	-0.552	Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	N
V/F	0.3608	ambiguous	0.3316	benign	-1.019	Destabilizing	0.967	D	0.819	deleterious	N	0.470625224	None	None	N
V/G	0.8213	likely_pathogenic	0.7946	pathogenic	-1.674	Destabilizing	0.983	D	0.85	deleterious	N	0.507015226	None	None	N
V/H	0.972	likely_pathogenic	0.967	pathogenic	-1.135	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
V/I	0.0674	likely_benign	0.068	benign	-0.553	Destabilizing	0.025	N	0.219	neutral	N	0.457281201	None	None	N
V/K	0.9647	likely_pathogenic	0.9557	pathogenic	-1.019	Destabilizing	0.987	D	0.855	deleterious	None	None	None	None	N
V/L	0.4101	ambiguous	0.4028	ambiguous	-0.553	Destabilizing	0.369	N	0.404	neutral	N	0.475829464	None	None	N
V/M	0.3319	likely_benign	0.3234	benign	-0.585	Destabilizing	0.975	D	0.732	prob.delet.	None	None	None	None	N
V/N	0.9219	likely_pathogenic	0.909	pathogenic	-0.865	Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
V/P	0.8571	likely_pathogenic	0.8087	pathogenic	-0.781	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
V/Q	0.9415	likely_pathogenic	0.9288	pathogenic	-0.959	Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	N
V/R	0.9528	likely_pathogenic	0.9432	pathogenic	-0.614	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
V/S	0.8478	likely_pathogenic	0.8289	pathogenic	-1.522	Destabilizing	0.987	D	0.837	deleterious	None	None	None	None	N
V/T	0.7421	likely_pathogenic	0.7226	pathogenic	-1.371	Destabilizing	0.916	D	0.643	neutral	None	None	None	None	N
V/W	0.957	likely_pathogenic	0.9508	pathogenic	-1.14	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
V/Y	0.8648	likely_pathogenic	0.8437	pathogenic	-0.844	Destabilizing	0.987	D	0.824	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.