TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30347	91264;91265;91266	chr2:178551861;178551860;178551859	chr2:179416588;179416587;179416586
N2AB	28706	86341;86342;86343	chr2:178551861;178551860;178551859	chr2:179416588;179416587;179416586
N2A	27779	83560;83561;83562	chr2:178551861;178551860;178551859	chr2:179416588;179416587;179416586
N2B	21282	64069;64070;64071	chr2:178551861;178551860;178551859	chr2:179416588;179416587;179416586
Novex-1	21407	64444;64445;64446	chr2:178551861;178551860;178551859	chr2:179416588;179416587;179416586
Novex-2	21474	64645;64646;64647	chr2:178551861;178551860;178551859	chr2:179416588;179416587;179416586
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-109
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.2806
• 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
A/T	None	None	0.884	D	0.36	0.186	0.35139820857	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
A/C	0.3826	ambiguous	0.3538	ambiguous	-0.972	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
A/D	0.2418	likely_benign	0.2468	benign	-1.28	Destabilizing	0.999	D	0.849	deleterious	N	0.494818082	None	None	N
A/E	0.1971	likely_benign	0.2011	benign	-1.261	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/F	0.2451	likely_benign	0.2515	benign	-0.909	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/G	0.1384	likely_benign	0.1385	benign	-1.182	Destabilizing	0.998	D	0.551	neutral	N	0.496895595	None	None	N
A/H	0.3879	ambiguous	0.3805	ambiguous	-1.265	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
A/I	0.1383	likely_benign	0.1343	benign	-0.236	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
A/K	0.3291	likely_benign	0.3378	benign	-1.253	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/L	0.1183	likely_benign	0.1114	benign	-0.236	Destabilizing	0.997	D	0.673	neutral	None	None	None	None	N
A/M	0.1494	likely_benign	0.1423	benign	-0.359	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
A/N	0.2048	likely_benign	0.2046	benign	-1.072	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/P	0.1273	likely_benign	0.1155	benign	-0.414	Destabilizing	1.0	D	0.839	deleterious	N	0.426990006	None	None	N
A/Q	0.2659	likely_benign	0.2637	benign	-1.146	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/R	0.3634	ambiguous	0.3728	ambiguous	-0.953	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
A/S	0.09	likely_benign	0.0887	benign	-1.412	Destabilizing	0.992	D	0.497	neutral	N	0.497452956	None	None	N
A/T	0.0767	likely_benign	0.075	benign	-1.279	Destabilizing	0.884	D	0.36	neutral	D	0.523754123	None	None	N
A/V	0.0869	likely_benign	0.0843	benign	-0.414	Destabilizing	0.996	D	0.584	neutral	N	0.515307998	None	None	N
A/W	0.6682	likely_pathogenic	0.6634	pathogenic	-1.279	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/Y	0.3485	ambiguous	0.3449	ambiguous	-0.847	Destabilizing	1.0	D	0.873	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.