TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29677	89254;89255;89256	chr2:178554082;178554081;178554080	chr2:179418809;179418808;179418807
N2AB	28036	84331;84332;84333	chr2:178554082;178554081;178554080	chr2:179418809;179418808;179418807
N2A	27109	81550;81551;81552	chr2:178554082;178554081;178554080	chr2:179418809;179418808;179418807
N2B	20612	62059;62060;62061	chr2:178554082;178554081;178554080	chr2:179418809;179418808;179418807
Novex-1	20737	62434;62435;62436	chr2:178554082;178554081;178554080	chr2:179418809;179418808;179418807
Novex-2	20804	62635;62636;62637	chr2:178554082;178554081;178554080	chr2:179418809;179418808;179418807
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-104
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2434
• 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
S/R	None	None	1.0	N	0.614	0.416	0.273070737957	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
S/A	0.1177	likely_benign	0.1279	benign	-0.483	Destabilizing	0.998	D	0.373	neutral	None	None	None	None	N
S/C	0.1348	likely_benign	0.1454	benign	-0.338	Destabilizing	1.0	D	0.693	prob.neutral	N	0.509654436	None	None	N
S/D	0.7757	likely_pathogenic	0.8297	pathogenic	0.64	Stabilizing	0.999	D	0.489	neutral	None	None	None	None	N
S/E	0.8617	likely_pathogenic	0.8908	pathogenic	0.565	Stabilizing	0.999	D	0.468	neutral	None	None	None	None	N
S/F	0.3742	ambiguous	0.4432	ambiguous	-0.968	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
S/G	0.1063	likely_benign	0.1106	benign	-0.616	Destabilizing	0.999	D	0.361	neutral	N	0.468666057	None	None	N
S/H	0.5288	ambiguous	0.558	ambiguous	-1.001	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
S/I	0.3342	likely_benign	0.4072	ambiguous	-0.261	Destabilizing	1.0	D	0.62	neutral	N	0.515984312	None	None	N
S/K	0.9096	likely_pathogenic	0.9275	pathogenic	-0.343	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
S/L	0.154	likely_benign	0.1819	benign	-0.261	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	N
S/M	0.252	likely_benign	0.2835	benign	-0.118	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
S/N	0.2248	likely_benign	0.2615	benign	-0.098	Destabilizing	0.999	D	0.454	neutral	N	0.518036085	None	None	N
S/P	0.8749	likely_pathogenic	0.9298	pathogenic	-0.305	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
S/Q	0.7028	likely_pathogenic	0.722	pathogenic	-0.293	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
S/R	0.8592	likely_pathogenic	0.8874	pathogenic	-0.196	Destabilizing	1.0	D	0.614	neutral	N	0.477431944	None	None	N
S/T	0.1098	likely_benign	0.1213	benign	-0.274	Destabilizing	0.999	D	0.339	neutral	N	0.504549499	None	None	N
S/V	0.2991	likely_benign	0.3543	ambiguous	-0.305	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
S/W	0.5779	likely_pathogenic	0.6437	pathogenic	-0.934	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
S/Y	0.2993	likely_benign	0.3498	ambiguous	-0.664	Destabilizing	1.0	D	0.703	prob.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.