ClinVar Miner

Submissions for variant NM_005921.2(MAP3K1):c.770C>T (p.Pro257Leu)

gnomAD frequency: 0.00001  dbSNP: rs56160159
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV000197066 SCV000255408 likely pathogenic 46,XY sex reversal 6 2013-05-14 criteria provided, single submitter clinical testing
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology RCV000197066 SCV002043746 uncertain significance 46,XY sex reversal 6 2021-07-05 criteria provided, single submitter clinical testing The c.770C>T variant is not present in publicly available population database like Exome Variant Server (EVS). The variant is present in 1000 Genomes, Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP including homozygotes. The heterozygous state of the variant is present in Indian Exome Database and in our in-house exome database at a low frequency. The variant was earlier reported to ClinVar, as likely pathogenic in similarly affected individuals [PMID: 11242112]. Predictions from different in-silico pathogenicity prediction programs like SIFT, PolyPhen-3, MutationTaster2, CADD, Varsome etc. are contradictory, however these predictions were not proved by established functional studies. Due to lack of enough evidence the variant has been calssified as uncertain significance.
Mendelics RCV002247625 SCV002518689 benign not specified 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000197066 SCV003302809 benign 46,XY sex reversal 6 2023-04-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004751363 SCV005344064 uncertain significance MAP3K1-related disorder 2024-03-26 no assertion criteria provided clinical testing The MAP3K1 c.770C>T variant is predicted to result in the amino acid substitution p.Pro257Leu. This variant has been reported in an individual with 46,XY sex reversal (Baxter et al. 2015. PubMed ID: 25383892). This variant is reported at elevated frequencies (0.43% of alleles, including four homozygotes) in individuals of South Asian descent in gnomAD but is rare in other defined subpopulations. Although we suspect that this variant may be benign, the clinical significance of this variant is classified as uncertain at this time due to insufficient functional and genetic evidence.

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