Submissions for variant NM_004530.6(MMP2):c.1627T>C (p.Tyr543His)

gnomAD frequency: 0.00010  dbSNP: rs369441378

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001116656	SCV001274770	uncertain significance	Multicentric osteolysis nodulosis arthropathy spectrum	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001308852	SCV001498326	uncertain significance	not provided	2022-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 543 of the MMP2 protein (p.Tyr543His). This variant is present in population databases (rs369441378, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 885202). 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 not expected to disrupt MMP2 protein function. 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.