TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2471	7636;7637;7638	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370
N2AB	2471	7636;7637;7638	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370
N2A	2471	7636;7637;7638	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370
N2B	2425	7498;7499;7500	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370
Novex-1	2425	7498;7499;7500	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370
Novex-2	2425	7498;7499;7500	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370
Novex-3	2471	7636;7637;7638	chr2:178773645;178773644;178773643	chr2:179638372;179638371;179638370

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-14
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.4823
• 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	rs1208886109	-0.442	0.31	N	0.267	0.188	0.241664281697	gnomAD-4.0.0	1.59073E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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	0.0962	likely_benign	0.0905	benign	-0.493	Destabilizing	0.134	N	0.269	neutral	N	0.49905219	None	None	N
P/C	0.7048	likely_pathogenic	0.7147	pathogenic	-0.723	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
P/D	0.5783	likely_pathogenic	0.6028	pathogenic	-0.297	Destabilizing	0.939	D	0.414	neutral	None	None	None	None	N
P/E	0.3846	ambiguous	0.4011	ambiguous	-0.41	Destabilizing	0.884	D	0.429	neutral	None	None	None	None	N
P/F	0.7483	likely_pathogenic	0.7625	pathogenic	-0.71	Destabilizing	0.997	D	0.565	neutral	None	None	None	None	N
P/G	0.3826	ambiguous	0.384	ambiguous	-0.621	Destabilizing	0.939	D	0.547	neutral	None	None	None	None	N
P/H	0.3389	likely_benign	0.3424	ambiguous	-0.176	Destabilizing	0.988	D	0.549	neutral	N	0.5071569	None	None	N
P/I	0.54	ambiguous	0.5494	ambiguous	-0.307	Destabilizing	0.991	D	0.571	neutral	None	None	None	None	N
P/K	0.4705	ambiguous	0.5028	ambiguous	-0.464	Destabilizing	0.884	D	0.451	neutral	None	None	None	None	N
P/L	0.2081	likely_benign	0.2106	benign	-0.307	Destabilizing	0.92	D	0.545	neutral	N	0.502277555	None	None	N
P/M	0.46	ambiguous	0.4576	ambiguous	-0.383	Destabilizing	0.997	D	0.547	neutral	None	None	None	None	N
P/N	0.4044	ambiguous	0.4098	ambiguous	-0.251	Destabilizing	0.939	D	0.517	neutral	None	None	None	None	N
P/Q	0.2114	likely_benign	0.213	benign	-0.493	Destabilizing	0.373	N	0.275	neutral	None	None	None	None	N
P/R	0.3509	ambiguous	0.3694	ambiguous	0.059	Stabilizing	0.976	D	0.521	neutral	N	0.506578377	None	None	N
P/S	0.1465	likely_benign	0.1432	benign	-0.615	Destabilizing	0.31	N	0.267	neutral	N	0.48830008	None	None	N
P/T	0.1475	likely_benign	0.1418	benign	-0.626	Destabilizing	0.852	D	0.447	neutral	N	0.485566884	None	None	N
P/V	0.3608	ambiguous	0.3582	ambiguous	-0.335	Destabilizing	0.939	D	0.547	neutral	None	None	None	None	N
P/W	0.8592	likely_pathogenic	0.8691	pathogenic	-0.779	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
P/Y	0.7102	likely_pathogenic	0.7299	pathogenic	-0.483	Destabilizing	0.997	D	0.567	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.