TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14117	42574;42575;42576	chr2:178634432;178634431;178634430	chr2:179499159;179499158;179499157
N2AB	12476	37651;37652;37653	chr2:178634432;178634431;178634430	chr2:179499159;179499158;179499157
N2A	11549	34870;34871;34872	chr2:178634432;178634431;178634430	chr2:179499159;179499158;179499157
N2B	5052	15379;15380;15381	chr2:178634432;178634431;178634430	chr2:179499159;179499158;179499157
Novex-1	5177	15754;15755;15756	chr2:178634432;178634431;178634430	chr2:179499159;179499158;179499157
Novex-2	5244	15955;15956;15957	chr2:178634432;178634431;178634430	chr2:179499159;179499158;179499157
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-91
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.7535
• 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
D/V	rs2060168886	None	0.942	N	0.637	0.172	0.313818047136	gnomAD-4.0.0	1.23209E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.61947E-05	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
D/A	0.2851	likely_benign	0.16	benign	-0.024	Destabilizing	0.698	D	0.453	neutral	N	0.450182824	None	None	N
D/C	0.8165	likely_pathogenic	0.6379	pathogenic	-0.011	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
D/E	0.2299	likely_benign	0.1536	benign	-0.227	Destabilizing	0.058	N	0.247	neutral	N	0.400477859	None	None	N
D/F	0.7847	likely_pathogenic	0.6304	pathogenic	-0.084	Destabilizing	0.978	D	0.651	neutral	None	None	None	None	N
D/G	0.2962	likely_benign	0.17	benign	-0.159	Destabilizing	0.698	D	0.452	neutral	N	0.440227003	None	None	N
D/H	0.4542	ambiguous	0.3038	benign	0.387	Stabilizing	0.992	D	0.468	neutral	N	0.465465983	None	None	N
D/I	0.6073	likely_pathogenic	0.386	ambiguous	0.266	Stabilizing	0.978	D	0.655	neutral	None	None	None	None	N
D/K	0.5483	ambiguous	0.3449	ambiguous	0.465	Stabilizing	0.86	D	0.435	neutral	None	None	None	None	N
D/L	0.5793	likely_pathogenic	0.376	ambiguous	0.266	Stabilizing	0.956	D	0.633	neutral	None	None	None	None	N
D/M	0.8055	likely_pathogenic	0.6325	pathogenic	0.175	Stabilizing	0.998	D	0.655	neutral	None	None	None	None	N
D/N	0.1572	likely_benign	0.1004	benign	0.226	Stabilizing	0.032	N	0.235	neutral	N	0.459005896	None	None	N
D/P	0.8684	likely_pathogenic	0.7202	pathogenic	0.19	Stabilizing	0.978	D	0.46	neutral	None	None	None	None	N
D/Q	0.5022	ambiguous	0.3377	benign	0.239	Stabilizing	0.956	D	0.403	neutral	None	None	None	None	N
D/R	0.565	likely_pathogenic	0.3984	ambiguous	0.662	Stabilizing	0.956	D	0.587	neutral	None	None	None	None	N
D/S	0.1747	likely_benign	0.1076	benign	0.124	Stabilizing	0.16	N	0.231	neutral	None	None	None	None	N
D/T	0.3976	ambiguous	0.2396	benign	0.234	Stabilizing	0.754	D	0.434	neutral	None	None	None	None	N
D/V	0.4354	ambiguous	0.256	benign	0.19	Stabilizing	0.942	D	0.637	neutral	N	0.485553859	None	None	N
D/W	0.9352	likely_pathogenic	0.869	pathogenic	-0.026	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
D/Y	0.4423	ambiguous	0.2885	benign	0.145	Stabilizing	0.99	D	0.652	neutral	D	0.580560376	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.