TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5658	17197;17198;17199	chr2:178731903;178731902;178731901	chr2:179596630;179596629;179596628
N2AB	5341	16246;16247;16248	chr2:178731903;178731902;178731901	chr2:179596630;179596629;179596628
N2A	4414	13465;13466;13467	chr2:178731903;178731902;178731901	chr2:179596630;179596629;179596628
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-40
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0626
• 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
A/S	None	None	0.425	N	0.587	0.131	0.146414634003	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
A/V	None	None	0.023	N	0.384	0.213	0.211220785272	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.4864	ambiguous	0.4309	ambiguous	-0.413	Destabilizing	0.003	N	0.291	neutral	None	None	None	None	N
A/D	0.9406	likely_pathogenic	0.9482	pathogenic	-1.747	Destabilizing	0.784	D	0.787	deleterious	N	0.500770115	None	None	N
A/E	0.9257	likely_pathogenic	0.9365	pathogenic	-1.499	Destabilizing	0.828	D	0.768	deleterious	None	None	None	None	N
A/F	0.8417	likely_pathogenic	0.862	pathogenic	-0.26	Destabilizing	0.944	D	0.819	deleterious	None	None	None	None	N
A/G	0.1415	likely_benign	0.1487	benign	-1.056	Destabilizing	0.001	N	0.293	neutral	N	0.390159627	None	None	N
A/H	0.9664	likely_pathogenic	0.9689	pathogenic	-1.742	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
A/I	0.5945	likely_pathogenic	0.6598	pathogenic	0.91	Stabilizing	0.543	D	0.701	prob.neutral	None	None	None	None	N
A/K	0.9806	likely_pathogenic	0.9837	pathogenic	-0.541	Destabilizing	0.828	D	0.751	deleterious	None	None	None	None	N
A/L	0.4876	ambiguous	0.5174	ambiguous	0.91	Stabilizing	0.329	N	0.685	prob.neutral	None	None	None	None	N
A/M	0.57	likely_pathogenic	0.6137	pathogenic	0.588	Stabilizing	0.944	D	0.781	deleterious	None	None	None	None	N
A/N	0.8832	likely_pathogenic	0.8933	pathogenic	-0.952	Destabilizing	0.893	D	0.791	deleterious	None	None	None	None	N
A/P	0.9358	likely_pathogenic	0.9503	pathogenic	0.476	Stabilizing	0.975	D	0.773	deleterious	N	0.500770115	None	None	N
A/Q	0.9298	likely_pathogenic	0.935	pathogenic	-0.638	Destabilizing	0.981	D	0.787	deleterious	None	None	None	None	N
A/R	0.961	likely_pathogenic	0.9662	pathogenic	-0.935	Destabilizing	0.944	D	0.786	deleterious	None	None	None	None	N
A/S	0.1974	likely_benign	0.1988	benign	-1.355	Destabilizing	0.425	N	0.587	neutral	N	0.470793924	None	None	N
A/T	0.1862	likely_benign	0.1956	benign	-0.959	Destabilizing	0.642	D	0.605	neutral	N	0.481664279	None	None	N
A/V	0.2592	likely_benign	0.2937	benign	0.476	Stabilizing	0.023	N	0.384	neutral	N	0.424133341	None	None	N
A/W	0.9766	likely_pathogenic	0.9803	pathogenic	-1.158	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
A/Y	0.9328	likely_pathogenic	0.9403	pathogenic	-0.452	Destabilizing	0.981	D	0.818	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.