TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23063	69412;69413;69414	chr2:178577148;178577147;178577146	chr2:179441875;179441874;179441873
N2AB	21422	64489;64490;64491	chr2:178577148;178577147;178577146	chr2:179441875;179441874;179441873
N2A	20495	61708;61709;61710	chr2:178577148;178577147;178577146	chr2:179441875;179441874;179441873
N2B	13998	42217;42218;42219	chr2:178577148;178577147;178577146	chr2:179441875;179441874;179441873
Novex-1	14123	42592;42593;42594	chr2:178577148;178577147;178577146	chr2:179441875;179441874;179441873
Novex-2	14190	42793;42794;42795	chr2:178577148;178577147;178577146	chr2:179441875;179441874;179441873
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-55
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4511
• 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
P/S	None	None	1.0	N	0.86	0.458	0.41219620536	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
P/A	0.071	likely_benign	0.0729	benign	-1.482	Destabilizing	1.0	D	0.818	deleterious	N	0.505573794	None	None	N
P/C	0.4857	ambiguous	0.4976	ambiguous	-1.019	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/D	0.5609	ambiguous	0.6024	pathogenic	-1.491	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/E	0.271	likely_benign	0.2892	benign	-1.44	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/F	0.5241	ambiguous	0.5611	ambiguous	-1.071	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/G	0.4238	ambiguous	0.4332	ambiguous	-1.816	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/H	0.2295	likely_benign	0.2527	benign	-1.223	Destabilizing	1.0	D	0.867	deleterious	N	0.513220197	None	None	N
P/I	0.2745	likely_benign	0.3242	benign	-0.64	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/K	0.2841	likely_benign	0.3007	benign	-1.293	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/L	0.1183	likely_benign	0.1338	benign	-0.64	Destabilizing	1.0	D	0.889	deleterious	N	0.51040904	None	None	N
P/M	0.2707	likely_benign	0.2893	benign	-0.632	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/N	0.4177	ambiguous	0.466	ambiguous	-1.19	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/Q	0.1562	likely_benign	0.1653	benign	-1.281	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/R	0.2029	likely_benign	0.2175	benign	-0.826	Destabilizing	1.0	D	0.907	deleterious	N	0.502255512	None	None	N
P/S	0.1476	likely_benign	0.1539	benign	-1.669	Destabilizing	1.0	D	0.86	deleterious	N	0.502002023	None	None	N
P/T	0.138	likely_benign	0.1543	benign	-1.497	Destabilizing	1.0	D	0.869	deleterious	N	0.500938839	None	None	N
P/V	0.1735	likely_benign	0.2019	benign	-0.889	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/W	0.7497	likely_pathogenic	0.7605	pathogenic	-1.269	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/Y	0.4879	ambiguous	0.5126	ambiguous	-0.972	Destabilizing	1.0	D	0.895	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.