ClinVar Miner

Submissions for variant NM_000044.6(AR):c.161TGC[5] (p.Leu57dup)

dbSNP: rs752055010
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001231121 SCV001403628 pathogenic Androgen resistance syndrome; Kennedy disease 2024-01-11 criteria provided, single submitter clinical testing This variant, c.170_172dup, results in the insertion of 1 amino acid(s) of the AR protein (p.Leu57dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs752055010, gnomAD 0.007%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with AR-related conditions (PMID: 25500996, 28261839; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as p.Leu57dup and p.57_58insLeu. ClinVar contains an entry for this variant (Variation ID: 958035). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV002249821 SCV002518491 pathogenic Malignant tumor of prostate 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004033116 SCV004906684 uncertain significance Inborn genetic diseases 2023-10-11 criteria provided, single submitter clinical testing The c.170_172dupTGC (p.L57dup) alteration, located in coding exon 1 of the AR gene. The alteration consists of an in-frame duplication of 3 nucleotides from position 170 to 172. This results in the duplication of a leucine residue at codon 57._x000D_ _x000D_ for AR-related androgen insensitivity syndrome; however, it is unlikely to be causative of AR-related spinal and bulbar muscular atrophy. Based on data from gnomAD, the c.170_172dupTGC allele has an overall frequency of 0.003% (6/174505) total alleles studied, with 2 hemizygotes observed. The highest observed frequency was 0.007% (1/14938) of African alleles. This variant has been reported in multiple individuals with features consistent with AR-related androgen insensitivity syndrome (Ferlin, 2006; Su, 2017; Liu, 2020), including a de novo occurrence (He, 2021). A functional study has demonstrated reduced cellular expression and transactivation activity in a luciferase assay (70% of wildtype) for p.L57dup (Tadokoro-Cuccaro, 2014). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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