Submissions for variant NM_000245.4(MET):c.4092G>A (p.Pro1364=)

gnomAD frequency: 0.34093  dbSNP: rs41737

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079494	SCV000111376	benign	not specified	2014-07-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162952	SCV000213439	benign	Hereditary cancer-predisposing syndrome	2014-11-19	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV000079494	SCV000306718	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000310007	SCV000466464	benign	Papillary renal cell carcinoma type 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000079494	SCV000513602	benign	not specified	2016-01-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001507221	SCV000623449	benign	Renal cell carcinoma	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589477	SCV000697663	benign	not provided	2016-08-18	criteria provided, single submitter	clinical testing	Variant summary: The MET c.4146G>A (p.Pro1382Pro) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant effect on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 51284/120730 (1/ no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of ***. However, these predictions have yet to be confirmed by functional studies. This variant was found in 51284/120730 control chromosomes (1/2, 11610 homozygotes), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic MET variant of 1/666666. In addition, multiple reputable clinical laboratories cite the variant as "benign." Therefore, the variant of interest has been classified as Benign.
Genome-Nilou Lab	RCV001775572	SCV002014201	benign	Autosomal recessive nonsyndromic hearing loss 97	2021-09-05	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000310007	SCV004015833	benign	Papillary renal cell carcinoma type 1	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589477	SCV005273296	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000079494	SCV001742820	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000079494	SCV001919465	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000079494	SCV001932654	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079494	SCV001952454	benign	not specified		no assertion criteria provided	clinical testing