ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.2935C>T (p.Arg979Ter)

dbSNP: rs769308802
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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 RCV001242306 SCV001415385 pathogenic Rhabdoid tumor predisposition syndrome 2 2022-10-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 967403). This premature translational stop signal has been observed in individual(s) with small cell carcinoma of the ovary, hypercalcemic type (PMID: 24658001, 28608987). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg979*) in the SMARCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMARCA4 are known to be pathogenic (PMID: 24658001, 24658002).
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269593 SCV001449687 likely pathogenic not provided 2017-10-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002436951 SCV002752432 pathogenic Hereditary cancer-predisposing syndrome 2017-12-06 criteria provided, single submitter clinical testing The p.R979* pathogenic mutation (also known as c.2935C>T), located in coding exon 19 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 2935. This changes the amino acid from an arginine to a stop codon within coding exon 19. This mutation has been reported in individuals diagnosed with small cell carcinoma of the ovary, hypercalcemic type, at ages 9 and 13; the latter of whom was also diagnosed with mild Coffin-Siris syndrome and congenital micropthalmia (Ramos P et al. Nat. Genet., 2014 May;46:427-9; Errichiello E et al. J. Pathol., 2017 Sep;243:9-15). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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