TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31499	94720;94721;94722	chr2:178547030;178547029;178547028	chr2:179411757;179411756;179411755
N2AB	29858	89797;89798;89799	chr2:178547030;178547029;178547028	chr2:179411757;179411756;179411755
N2A	28931	87016;87017;87018	chr2:178547030;178547029;178547028	chr2:179411757;179411756;179411755
N2B	22434	67525;67526;67527	chr2:178547030;178547029;178547028	chr2:179411757;179411756;179411755
Novex-1	22559	67900;67901;67902	chr2:178547030;178547029;178547028	chr2:179411757;179411756;179411755
Novex-2	22626	68101;68102;68103	chr2:178547030;178547029;178547028	chr2:179411757;179411756;179411755
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-117
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.8425
• Predicted PPI site: I

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
R/I	None	None	0.999	N	0.779	0.404	0.375861065471	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.64	likely_pathogenic	0.6778	pathogenic	0.086	Stabilizing	0.998	D	0.655	prob.neutral	None	None	None	None	I
R/C	0.3679	ambiguous	0.407	ambiguous	-0.218	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
R/D	0.8501	likely_pathogenic	0.867	pathogenic	-0.265	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	I
R/E	0.628	likely_pathogenic	0.6631	pathogenic	-0.218	Destabilizing	0.998	D	0.693	prob.delet.	None	None	None	None	I
R/F	0.7373	likely_pathogenic	0.7646	pathogenic	-0.23	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
R/G	0.4988	ambiguous	0.543	ambiguous	-0.062	Destabilizing	0.999	D	0.68	prob.neutral	N	0.417717162	None	None	I
R/H	0.1866	likely_benign	0.2053	benign	-0.594	Destabilizing	0.999	D	0.738	deleterious	None	None	None	None	I
R/I	0.5141	ambiguous	0.5441	ambiguous	0.431	Stabilizing	0.999	D	0.779	deleterious	N	0.478802906	None	None	I
R/K	0.1267	likely_benign	0.1347	benign	-0.11	Destabilizing	0.994	D	0.634	neutral	N	0.375523822	None	None	I
R/L	0.4137	ambiguous	0.4475	ambiguous	0.431	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
R/M	0.5399	ambiguous	0.5805	pathogenic	-0.051	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
R/N	0.8057	likely_pathogenic	0.8265	pathogenic	-0.043	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	I
R/P	0.6237	likely_pathogenic	0.6402	pathogenic	0.335	Stabilizing	0.999	D	0.736	deleterious	None	None	None	None	I
R/Q	0.1832	likely_benign	0.2	benign	-0.066	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
R/S	0.7332	likely_pathogenic	0.7664	pathogenic	-0.217	Destabilizing	0.999	D	0.765	deleterious	N	0.436974926	None	None	I
R/T	0.5657	likely_pathogenic	0.6037	pathogenic	-0.057	Destabilizing	0.999	D	0.759	deleterious	N	0.448402641	None	None	I
R/V	0.5844	likely_pathogenic	0.6119	pathogenic	0.335	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
R/W	0.3133	likely_benign	0.3473	ambiguous	-0.418	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
R/Y	0.5718	likely_pathogenic	0.5979	pathogenic	None	Stabilizing	0.999	D	0.767	deleterious	None	None	None	None	I

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.