TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16117	48574;48575;48576	chr2:178615752;178615751;178615750	chr2:179480479;179480478;179480477
N2AB	14476	43651;43652;43653	chr2:178615752;178615751;178615750	chr2:179480479;179480478;179480477
N2A	13549	40870;40871;40872	chr2:178615752;178615751;178615750	chr2:179480479;179480478;179480477
N2B	7052	21379;21380;21381	chr2:178615752;178615751;178615750	chr2:179480479;179480478;179480477
Novex-1	7177	21754;21755;21756	chr2:178615752;178615751;178615750	chr2:179480479;179480478;179480477
Novex-2	7244	21955;21956;21957	chr2:178615752;178615751;178615750	chr2:179480479;179480478;179480477
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-4
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.3616
• 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
P/A	None	None	0.002	N	0.189	0.118	0.146414634003	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
P/L	None	None	0.379	N	0.495	0.258	0.52586976336	gnomAD-4.0.0	1.59514E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4346E-05	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
P/A	0.0873	likely_benign	0.1023	benign	-1.054	Destabilizing	0.002	N	0.189	neutral	N	0.467776596	None	None	N
P/C	0.4169	ambiguous	0.5056	ambiguous	-0.928	Destabilizing	0.977	D	0.555	neutral	None	None	None	None	N
P/D	0.4007	ambiguous	0.4407	ambiguous	-0.634	Destabilizing	0.617	D	0.429	neutral	None	None	None	None	N
P/E	0.266	likely_benign	0.2852	benign	-0.663	Destabilizing	0.617	D	0.441	neutral	None	None	None	None	N
P/F	0.4991	ambiguous	0.5676	pathogenic	-0.857	Destabilizing	0.92	D	0.569	neutral	None	None	None	None	N
P/G	0.2222	likely_benign	0.2469	benign	-1.316	Destabilizing	0.25	N	0.447	neutral	None	None	None	None	N
P/H	0.1802	likely_benign	0.2095	benign	-0.709	Destabilizing	0.99	D	0.535	neutral	N	0.474290641	None	None	N
P/I	0.3471	ambiguous	0.4076	ambiguous	-0.464	Destabilizing	0.85	D	0.555	neutral	None	None	None	None	N
P/K	0.236	likely_benign	0.2662	benign	-0.908	Destabilizing	0.617	D	0.429	neutral	None	None	None	None	N
P/L	0.1269	likely_benign	0.1522	benign	-0.464	Destabilizing	0.379	N	0.495	neutral	N	0.463903402	None	None	N
P/M	0.2762	likely_benign	0.342	ambiguous	-0.514	Destabilizing	0.972	D	0.539	neutral	None	None	None	None	N
P/N	0.2623	likely_benign	0.304	benign	-0.749	Destabilizing	0.617	D	0.522	neutral	None	None	None	None	N
P/Q	0.152	likely_benign	0.1719	benign	-0.9	Destabilizing	0.92	D	0.534	neutral	None	None	None	None	N
P/R	0.1675	likely_benign	0.1846	benign	-0.388	Destabilizing	0.81	D	0.553	neutral	N	0.446093752	None	None	N
P/S	0.112	likely_benign	0.1263	benign	-1.248	Destabilizing	0.007	N	0.185	neutral	N	0.386471922	None	None	N
P/T	0.0926	likely_benign	0.1046	benign	-1.154	Destabilizing	0.007	N	0.186	neutral	N	0.338847992	None	None	N
P/V	0.2251	likely_benign	0.2674	benign	-0.624	Destabilizing	0.447	N	0.485	neutral	None	None	None	None	N
P/W	0.6012	likely_pathogenic	0.6673	pathogenic	-0.975	Destabilizing	0.992	D	0.617	neutral	None	None	None	None	N
P/Y	0.4272	ambiguous	0.4927	ambiguous	-0.687	Destabilizing	0.972	D	0.566	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.