ClinVar Miner

Submissions for variant NM_002294.3(LAMP2):c.1040C>G (p.Thr347Ser)

dbSNP: rs730880487
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767120 SCV000207910 uncertain significance not provided 2016-06-30 criteria provided, single submitter clinical testing p.Thr347Ser (T347S) ACC>AGC: c.1040 C>G in exon 8 of the LAMP2 gene (NM_002294.2). The Thr347Ser variant in the LAMP2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Thr347Ser variant was not observed in approximately 5,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although Thr347Ser results in a conservative amino acid substitution of one neutral, polar residue for another, this substitution occurs at a position that is highly conserved across species. In silico algorithms are not consistent in their predictions, but at least two concur that Thr347Ser is possibly damaging to the protein structure/function. However, mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. With the clinical and molecular information available at this time, we cannot definitively determine if Thr347Ser is a disease-causing mutation or a rare benign variant. This result cannot be interpreted for diagnosis or used for family member screening at this time. Clinical correlation with this test result is recommended. The variant is found in HCM panel(s).
Ambry Genetics RCV002390375 SCV002702063 uncertain significance Cardiovascular phenotype 2022-01-07 criteria provided, single submitter clinical testing The p.T347S variant (also known as c.1040C>G), located in coding exon 8 of the LAMP2 gene, results from a C to G substitution at nucleotide position 1040. The threonine at codon 347 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003509504 SCV004282979 uncertain significance Danon disease 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 347 of the LAMP2 protein (p.Thr347Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 180879). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LAMP2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000157975 SCV000280172 uncertain significance not specified 2015-03-12 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. LAMP2 p.Thr347Ser Based on the data reviewed below we consider this variant a variant of uncertain significance. This variant is novel. p.Thr347Ser results in a conservative amino acid substitution of one neutral, polar residue for another. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. Mutation Taster predicts this variant to be disease-causing. The Threonine at codon 347 is conserved across species, as are neighboring amino acids. No other variants have been reported in association with disease at this codon or at nearby codons. In total the variant has not been seen in ~6,500 individuals from publicly available population datasets. There is no variation at codon 347 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 1/3/14). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 1/3/14).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.