TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1894	5905;5906;5907	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909
N2AB	1894	5905;5906;5907	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909
N2A	1894	5905;5906;5907	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909
N2B	1848	5767;5768;5769	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909
Novex-1	1848	5767;5768;5769	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909
Novex-2	1848	5767;5768;5769	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909
Novex-3	1894	5905;5906;5907	chr2:178776184;178776183;178776182	chr2:179640911;179640910;179640909

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-9
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.1964
• 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/V	rs751529942	-1.212	0.993	N	0.338	0.292	0.664580999671	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.53E-05	None	0	0	0
I/V	rs751529942	-1.212	0.993	N	0.338	0.292	0.664580999671	gnomAD-4.0.0	6.36215E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73082E-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	0.9646	likely_pathogenic	0.9682	pathogenic	-2.207	Highly Destabilizing	0.999	D	0.525	neutral	None	None	None	None	N
I/C	0.9804	likely_pathogenic	0.9837	pathogenic	-1.036	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
I/D	0.9956	likely_pathogenic	0.9956	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
I/E	0.9889	likely_pathogenic	0.9895	pathogenic	-2.124	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
I/F	0.6383	likely_pathogenic	0.6403	pathogenic	-1.447	Destabilizing	1.0	D	0.742	deleterious	N	0.514848004	None	None	N
I/G	0.9935	likely_pathogenic	0.994	pathogenic	-2.654	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
I/H	0.9833	likely_pathogenic	0.9839	pathogenic	-2.038	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
I/K	0.9851	likely_pathogenic	0.984	pathogenic	-1.559	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
I/L	0.3743	ambiguous	0.3951	ambiguous	-0.952	Destabilizing	0.993	D	0.357	neutral	N	0.491818601	None	None	N
I/M	0.3913	ambiguous	0.4092	ambiguous	-0.564	Destabilizing	1.0	D	0.734	prob.delet.	N	0.504185326	None	None	N
I/N	0.9217	likely_pathogenic	0.9262	pathogenic	-1.664	Destabilizing	1.0	D	0.789	deleterious	N	0.499914249	None	None	N
I/P	0.9944	likely_pathogenic	0.9945	pathogenic	-1.348	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
I/Q	0.9778	likely_pathogenic	0.9794	pathogenic	-1.67	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
I/R	0.9768	likely_pathogenic	0.9753	pathogenic	-1.105	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
I/S	0.947	likely_pathogenic	0.9509	pathogenic	-2.282	Highly Destabilizing	1.0	D	0.755	deleterious	N	0.500082925	None	None	N
I/T	0.9107	likely_pathogenic	0.9206	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.725	prob.delet.	N	0.462323146	None	None	N
I/V	0.2662	likely_benign	0.2841	benign	-1.348	Destabilizing	0.993	D	0.338	neutral	N	0.487476483	None	None	N
I/W	0.979	likely_pathogenic	0.9795	pathogenic	-1.81	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
I/Y	0.9172	likely_pathogenic	0.9182	pathogenic	-1.499	Destabilizing	1.0	D	0.799	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.