TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2572	7939;7940;7941	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975
N2AB	2572	7939;7940;7941	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975
N2A	2572	7939;7940;7941	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975
N2B	2526	7801;7802;7803	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975
Novex-1	2526	7801;7802;7803	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975
Novex-2	2526	7801;7802;7803	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975
Novex-3	2572	7939;7940;7941	chr2:178773250;178773249;178773248	chr2:179637977;179637976;179637975

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-15
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.124
• 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
I/M	rs749818939	-1.133	0.171	D	0.589	0.187	0.239305524855	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/M	rs749818939	-1.133	0.171	D	0.589	0.187	0.239305524855	gnomAD-4.0.0	3.42082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.79764E-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
I/A	0.8586	likely_pathogenic	0.8676	pathogenic	-2.434	Highly Destabilizing	0.016	N	0.448	neutral	None	None	None	None	N
I/C	0.9049	likely_pathogenic	0.9067	pathogenic	-1.675	Destabilizing	0.628	D	0.639	neutral	None	None	None	None	N
I/D	0.9874	likely_pathogenic	0.9864	pathogenic	-2.785	Highly Destabilizing	0.038	N	0.651	neutral	None	None	None	None	N
I/E	0.9573	likely_pathogenic	0.9545	pathogenic	-2.557	Highly Destabilizing	0.038	N	0.639	neutral	None	None	None	None	N
I/F	0.4729	ambiguous	0.4435	ambiguous	-1.547	Destabilizing	0.029	N	0.548	neutral	D	0.669784217	None	None	N
I/G	0.9666	likely_pathogenic	0.9688	pathogenic	-2.964	Highly Destabilizing	0.038	N	0.619	neutral	None	None	None	None	N
I/H	0.9538	likely_pathogenic	0.9486	pathogenic	-2.41	Highly Destabilizing	0.214	N	0.652	neutral	None	None	None	None	N
I/K	0.9098	likely_pathogenic	0.9044	pathogenic	-1.941	Destabilizing	0.038	N	0.633	neutral	None	None	None	None	N
I/L	0.0774	likely_benign	0.0803	benign	-0.902	Destabilizing	None	N	0.085	neutral	N	0.454773622	None	None	N
I/M	0.1457	likely_benign	0.1434	benign	-0.782	Destabilizing	0.171	N	0.589	neutral	D	0.576059896	None	None	N
I/N	0.869	likely_pathogenic	0.8597	pathogenic	-2.278	Highly Destabilizing	None	N	0.471	neutral	D	0.671295168	None	None	N
I/P	0.9686	likely_pathogenic	0.9688	pathogenic	-1.394	Destabilizing	0.356	N	0.697	prob.neutral	None	None	None	None	N
I/Q	0.9181	likely_pathogenic	0.9113	pathogenic	-2.141	Highly Destabilizing	0.214	N	0.681	prob.neutral	None	None	None	None	N
I/R	0.8816	likely_pathogenic	0.8754	pathogenic	-1.696	Destabilizing	0.214	N	0.697	prob.neutral	None	None	None	None	N
I/S	0.9211	likely_pathogenic	0.917	pathogenic	-2.934	Highly Destabilizing	0.029	N	0.601	neutral	D	0.67042108	None	None	N
I/T	0.8664	likely_pathogenic	0.8679	pathogenic	-2.552	Highly Destabilizing	0.012	N	0.533	neutral	D	0.625764503	None	None	N
I/V	0.1576	likely_benign	0.1563	benign	-1.394	Destabilizing	None	N	0.105	neutral	N	0.511025572	None	None	N
I/W	0.9455	likely_pathogenic	0.938	pathogenic	-1.909	Destabilizing	0.864	D	0.661	neutral	None	None	None	None	N
I/Y	0.8413	likely_pathogenic	0.8286	pathogenic	-1.594	Destabilizing	0.356	N	0.673	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.