TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6734	20425;20426;20427	chr2:178727165;178727164;178727163	chr2:179591892;179591891;179591890
N2AB	6417	19474;19475;19476	chr2:178727165;178727164;178727163	chr2:179591892;179591891;179591890
N2A	5490	16693;16694;16695	chr2:178727165;178727164;178727163	chr2:179591892;179591891;179591890
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-51
• Domain position: 68
• Structural Position: 149
• Q(SASA): 0.1878
• 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
D/E	rs2079483133	None	0.079	D	0.318	0.612	0.415313616471	gnomAD-4.0.0	1.3701E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80057E-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
D/A	0.7573	likely_pathogenic	0.8408	pathogenic	-0.349	Destabilizing	0.996	D	0.8	deleterious	D	0.614851908	None	None	N
D/C	0.9627	likely_pathogenic	0.9736	pathogenic	-0.091	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/E	0.5861	likely_pathogenic	0.6271	pathogenic	-0.737	Destabilizing	0.079	N	0.318	neutral	D	0.57556608	None	None	N
D/F	0.936	likely_pathogenic	0.9672	pathogenic	0.242	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
D/G	0.7833	likely_pathogenic	0.8667	pathogenic	-0.746	Destabilizing	0.994	D	0.765	deleterious	D	0.652432222	None	None	N
D/H	0.8014	likely_pathogenic	0.8916	pathogenic	-0.021	Destabilizing	1.0	D	0.842	deleterious	D	0.58298463	None	None	N
D/I	0.9086	likely_pathogenic	0.9477	pathogenic	0.713	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
D/K	0.9429	likely_pathogenic	0.9681	pathogenic	0.114	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/L	0.9215	likely_pathogenic	0.9554	pathogenic	0.713	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
D/M	0.9519	likely_pathogenic	0.9723	pathogenic	1.152	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/N	0.4562	ambiguous	0.5761	pathogenic	-0.699	Destabilizing	0.997	D	0.791	deleterious	D	0.60905851	None	None	N
D/P	0.9945	likely_pathogenic	0.9972	pathogenic	0.385	Stabilizing	0.994	D	0.827	deleterious	None	None	None	None	N
D/Q	0.905	likely_pathogenic	0.9402	pathogenic	-0.477	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
D/R	0.9635	likely_pathogenic	0.9802	pathogenic	0.197	Stabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
D/S	0.6857	likely_pathogenic	0.7851	pathogenic	-0.912	Destabilizing	0.997	D	0.667	neutral	None	None	None	None	N
D/T	0.8711	likely_pathogenic	0.9209	pathogenic	-0.54	Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
D/V	0.7999	likely_pathogenic	0.874	pathogenic	0.385	Stabilizing	0.999	D	0.883	deleterious	D	0.65283583	None	None	N
D/W	0.9912	likely_pathogenic	0.9957	pathogenic	0.486	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/Y	0.6757	likely_pathogenic	0.802	pathogenic	0.551	Stabilizing	1.0	D	0.884	deleterious	D	0.636614665	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.