TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18212	54859;54860;54861	chr2:178604053;178604052;178604051	chr2:179468780;179468779;179468778
N2AB	16571	49936;49937;49938	chr2:178604053;178604052;178604051	chr2:179468780;179468779;179468778
N2A	15644	47155;47156;47157	chr2:178604053;178604052;178604051	chr2:179468780;179468779;179468778
N2B	9147	27664;27665;27666	chr2:178604053;178604052;178604051	chr2:179468780;179468779;179468778
Novex-1	9272	28039;28040;28041	chr2:178604053;178604052;178604051	chr2:179468780;179468779;179468778
Novex-2	9339	28240;28241;28242	chr2:178604053;178604052;178604051	chr2:179468780;179468779;179468778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-20
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7898
• 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
Y/F	rs772610346	None	0.999	N	0.55	0.293	0.474643619859	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

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
Y/A	0.463	ambiguous	0.4493	ambiguous	-0.742	Destabilizing	1.0	D	0.561	neutral	None	None	None	None	N
Y/C	0.2179	likely_benign	0.2168	benign	-0.074	Destabilizing	1.0	D	0.686	prob.neutral	N	0.509013957	None	None	N
Y/D	0.5331	ambiguous	0.5336	ambiguous	0.745	Stabilizing	1.0	D	0.694	prob.neutral	N	0.421122826	None	None	N
Y/E	0.7609	likely_pathogenic	0.7641	pathogenic	0.749	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
Y/F	0.1036	likely_benign	0.1018	benign	-0.286	Destabilizing	0.999	D	0.55	neutral	N	0.489985479	None	None	N
Y/G	0.4441	ambiguous	0.4383	ambiguous	-0.933	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
Y/H	0.2873	likely_benign	0.2759	benign	0.225	Stabilizing	1.0	D	0.597	neutral	N	0.447445423	None	None	N
Y/I	0.4992	ambiguous	0.4879	ambiguous	-0.245	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
Y/K	0.7256	likely_pathogenic	0.7385	pathogenic	0.013	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	N
Y/L	0.4644	ambiguous	0.4401	ambiguous	-0.245	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
Y/M	0.6547	likely_pathogenic	0.6575	pathogenic	-0.269	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
Y/N	0.2987	likely_benign	0.2908	benign	-0.294	Destabilizing	1.0	D	0.655	neutral	N	0.429609023	None	None	N
Y/P	0.8119	likely_pathogenic	0.8119	pathogenic	-0.394	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
Y/Q	0.5982	likely_pathogenic	0.5859	pathogenic	-0.187	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
Y/R	0.4948	ambiguous	0.492	ambiguous	0.217	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	N
Y/S	0.269	likely_benign	0.2585	benign	-0.689	Destabilizing	1.0	D	0.641	neutral	N	0.401208914	None	None	N
Y/T	0.4736	ambiguous	0.4815	ambiguous	-0.596	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
Y/V	0.3689	ambiguous	0.3599	ambiguous	-0.394	Destabilizing	1.0	D	0.57	neutral	None	None	None	None	N
Y/W	0.4124	ambiguous	0.4149	ambiguous	-0.361	Destabilizing	1.0	D	0.625	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.