NM_003140.2(SRY):c.270C>G (p.Ile90Met) AND 46,XY sex reversal, type 1

Clinical significance:Pathogenic (Last evaluated: Apr 1, 2003)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_003140.2(SRY):c.270C>G (p.Ile90Met)]

NM_003140.2(SRY):c.270C>G (p.Ile90Met)

SRY:sex determining region Y [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_003140.2(SRY):c.270C>G (p.Ile90Met)
  • NC_000024.10:g.2787334G>C
  • NG_011751.1:g.5418C>G
  • NM_003140.2:c.270C>G
  • NP_003131.1:p.Ile90Met
  • NC_000024.9:g.2655375G>C
  • NM_003140.1:c.270C>G
  • Q05066:p.Ile90Met
Protein change:
UniProtKB: Q05066#VAR_003724; OMIM: 480000.0006; dbSNP: 104894959
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_003140.2:c.270C>G - missense variant - [Sequence Ontology: SO:0001583]


46,XY sex reversal, type 1 (SRXY1)
46,XY SEX REVERSAL, SRY-RELATED; SRY-related 46,XY complete gonadal dysgenesis
MedGen: C2748896; Orphanet: 242; OMIM: 400044

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000030620OMIMno assertion criteria providedPathogenic
(Apr 1, 2003)
germlineliterature only

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation.

Berkovitz GD, Fechner PY, Zacur HW, Rock JA, Snyder HM 3rd, Migeon CJ, Perlman EJ.

Medicine (Baltimore). 1991 Nov;70(6):375-83.

PubMed [citation]

DNA binding activity of recombinant SRY from normal males and XY females.

Harley VR, Jackson DI, Hextall PJ, Hawkins JR, Berkovitz GD, Sockanathan S, Lovell-Badge R, Goodfellow PN.

Science. 1992 Jan 24;255(5043):453-6.

PubMed [citation]
See all PubMed Citations (8)

Details of each submission

From OMIM, SCV000030620.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (8)


In 'patient 213' (patient 4 in the report of Berkovitz et al., 1991), a phenotypic female with complete gonadal dysgenesis and a 46,XY karyotype (SRXY1; 400044), Hawkins et al. (1992) identified a C-G transversion at nucleotide 680, causing an isoleucine-to-methionine amino acid substitution within the HMG box. The father and brother of patient 213 also carried the mutation, which was not found in 78 ethnically matched unrelated males. The authors noted that in vitro studies by Harley et al. (1992) demonstrated that the I90M mutant had reduced DNA-binding activity.

Dork et al. (1998) observed this mutation in a patient unrelated to that reported by Hawkins et al. (1992). None of the previously reviewed mutations had been observed in more than a single family. In 3 cases, however, fertile fathers were found to share the same SRY mutation with their sex-reversed daughters (Berta et al., 1990; Jager et al., 1992; Vilain et al., 1992). In the absence of mosaicism, there are plausible explanations for these familiar variants. The variant could fortuitously occur in a family segregating for a different sex-reversing gene, or the variant may predispose toward sex reversal and cause a differentiation effect only in association with other genetic or environmental factors. In the case reported by Hawkins et al. (1992), I90M was likewise associated with complete gonadal dysgenesis in the proband but was also present in normal relatives of the patient, including the father. Thus, Dork et al. (1998) concluded that this appears to be an instance of a Y-linked inherited disorder with incomplete penetrance and suggested that identification of unrelated individuals carrying the I90M mutation may help to elucidate the mechanism.

Maier et al. (2003) reported a 46,XY true hermaphrodite (see 400044) who had the I90M mutation in the SRY gene. The father, 3 uncles, and an older brother carried the identical mutation without phenotypic effects. Maier et al. (2003) concluded that the mutated protein retained enough activity to allow normal development in some individuals.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 5, 2017