TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23979	72160;72161;72162	chr2:178574197;178574196;178574195	chr2:179438924;179438923;179438922
N2AB	22338	67237;67238;67239	chr2:178574197;178574196;178574195	chr2:179438924;179438923;179438922
N2A	21411	64456;64457;64458	chr2:178574197;178574196;178574195	chr2:179438924;179438923;179438922
N2B	14914	44965;44966;44967	chr2:178574197;178574196;178574195	chr2:179438924;179438923;179438922
Novex-1	15039	45340;45341;45342	chr2:178574197;178574196;178574195	chr2:179438924;179438923;179438922
Novex-2	15106	45541;45542;45543	chr2:178574197;178574196;178574195	chr2:179438924;179438923;179438922
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-62
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0639
• 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/L	None	None	0.426	N	0.333	0.213	0.321108458156	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
I/V	rs2154171370	None	0.011	N	0.203	0.126	0.347438807231	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.8423	likely_pathogenic	0.843	pathogenic	-1.945	Destabilizing	0.845	D	0.473	neutral	None	None	None	None	N
I/C	0.8527	likely_pathogenic	0.8473	pathogenic	-1.17	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
I/D	0.976	likely_pathogenic	0.9755	pathogenic	-1.682	Destabilizing	0.996	D	0.773	deleterious	None	None	None	None	N
I/E	0.9618	likely_pathogenic	0.9583	pathogenic	-1.438	Destabilizing	0.987	D	0.753	deleterious	None	None	None	None	N
I/F	0.5833	likely_pathogenic	0.5845	pathogenic	-1.037	Destabilizing	0.967	D	0.583	neutral	N	0.482458374	None	None	N
I/G	0.9621	likely_pathogenic	0.9623	pathogenic	-2.504	Highly Destabilizing	0.987	D	0.742	deleterious	None	None	None	None	N
I/H	0.918	likely_pathogenic	0.9102	pathogenic	-1.99	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
I/K	0.9146	likely_pathogenic	0.9032	pathogenic	-1.127	Destabilizing	0.987	D	0.755	deleterious	None	None	None	None	N
I/L	0.2295	likely_benign	0.2274	benign	-0.339	Destabilizing	0.426	N	0.333	neutral	N	0.493217785	None	None	N
I/M	0.3125	likely_benign	0.3166	benign	-0.39	Destabilizing	0.983	D	0.585	neutral	N	0.482458374	None	None	N
I/N	0.7393	likely_pathogenic	0.7281	pathogenic	-1.459	Destabilizing	0.994	D	0.779	deleterious	N	0.474541428	None	None	N
I/P	0.9487	likely_pathogenic	0.9468	pathogenic	-0.853	Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	N
I/Q	0.9209	likely_pathogenic	0.9091	pathogenic	-1.25	Destabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
I/R	0.8773	likely_pathogenic	0.8617	pathogenic	-1.103	Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	N
I/S	0.7999	likely_pathogenic	0.8	pathogenic	-2.236	Highly Destabilizing	0.983	D	0.685	prob.neutral	N	0.506605583	None	None	N
I/T	0.7174	likely_pathogenic	0.7087	pathogenic	-1.83	Destabilizing	0.892	D	0.599	neutral	N	0.509701816	None	None	N
I/V	0.0926	likely_benign	0.0965	benign	-0.853	Destabilizing	0.011	N	0.203	neutral	N	0.392341501	None	None	N
I/W	0.9827	likely_pathogenic	0.9811	pathogenic	-1.369	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
I/Y	0.9078	likely_pathogenic	0.8951	pathogenic	-1.013	Destabilizing	0.987	D	0.709	prob.delet.	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.